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  • 1980-1984  (597)
  • 1980  (597)
  • Computational Chemistry and Molecular Modeling  (333)
  • Ultrastructure  (122)
  • Rat  (88)
  • Nuclear reactions
  • pharmacokinetics
Material
Years
  • 1980-1984  (597)
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 385 (1980), S. 283-291 
    ISSN: 1432-2307
    Keywords: Hodgkin's disease ; Myofibroblasts ; Ultrastructure ; Nodular sclerosis ; Host response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten cases of nodular sclerosing Hodgkin's disease involving lymph nodes were studied by electron microscopy to determine the ultrastructural composition of the nodule-stromal interphase and the collagenized regions. In addition to a few lymphocytes, rare eosinophils and neutrophils, abundant filamentous and granular electron dense material, collagen fibers and myofibroblasts were observed in all instances. Since myofibroblasts possess contractile and synthetic properties, it is likely they contribute to the retraction and sclerosis which together represent one of the morphologic hallmarks of the disease. The dense fibrosis and contractile state of such tissue may constitute a beneficial host response to contain and limit local and vascular invasion by the neoplastic cellular population, thus contributing to the relative benignity of this form of Hodgkin's disease.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Parathyroid carcinoma ; Tumour progession ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of parathyroid carcinoma in a 74-year-old female patient was studied by light and electron microscopy. The malignancy of the parathyroid tumour was confirmed by local recurrence and infiltration of adjacent structures. The tumour was composed of uniform chief cells without mitoses. Ultrastructurally, the cells were characterized by tortuous plasma membranes, numerous secretion granules, an extensive rough endoplasmic reticulum and lack of lipid vacuoles, all indicating hyperactivity, but not malignancy. At death, the autopsy revealed local recurrence of tumour tissue, but no distant metastases. Both light and electron microscopy showed that considerable dedifferentiation of the tumour tissue had occurred. The tumour cells were now characterized by a marked nuclear pleomorphism and a coarse clumping of the chromatin. The presence of secretion granules alone suggested a parathyroid origin. Thus, at death there was unequivocal histological evidence of a carcinoma, whereas no such diagnosis could be made from the early biopsy. The clinical course alone indicated the malignant nature of the lesion.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Pituitary adenoma ; Prolactin ; Ultrastructure ; Immunohistochemistry ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fifteen cases of pituitary adenoma, 14 of which were associated with hyperprolactinemia, were studied by observation and granule morphometry of electron micrographs, immunohistochemistry and sequential observation of in vitro release with regard to hormone production, storage and secretion. Adenoma cells of 6 cases with marked elevation of plasma prolactin were sparsely granulated, showed characteristic ultrastrucures including the presence of small secretory granules, well developed Golgi and rough membranes, misplaced exocytosis, and positive or negative immunostaining for prolactin. These adenomas also showed vigorous release of the hormone into the circulation and/or culture medium. In vitro studies showed that negative immunostaining of adenoma cells did not preclude the production and secretion of the hormone. One densely granulated adenoma containing cells with numerous lactotroph type granules showed moderate release of prolactin into the circulation. In an acromegalic case associated with both high plasma growth hormone and prolactin, some cells were shown by immunohistochemistry to store both hormones. There were 4 adenomas which could not be shown to produce, store and secrete prolactin by any method available.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 387 (1980), S. 279-288 
    ISSN: 1432-2307
    Keywords: Pituitary ; Ultrastructure ; Hypophysectomy ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar rats were partially hypophysectomized and sacrificed at intervals of from 2 days to 1 year following the operation. The resected material was examined under the light microscope and the residual pituitary under the light and electron microscope. Neither regeneration nor an anatomical restoration of the adenohypophysis occurred even one year after partial hypophysectomy. An increased number of small chromophobe stem cells and juvenile chromophil cells were found in the residual pituitary. The amount of mitoses were not significantly increased. The ACTH, FSH and prolactin producing cells demonstrated electron microscopically distinct changes which were interpreted as signs of intensified activity. This can be seen as a “functional regeneration” to maintain vital pituitary function for the organism.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 387 (1980), S. 353-369 
    ISSN: 1432-2307
    Keywords: Granulosa cell tumors ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural features of three granulosa cell tumors are presented. The neoplastic non-luteinized granulosa cells are characterized at sub-microscopical level by severely indented nuclei with prominent nucleoli, sparse to moderately developed predominantly granular endoplasmic reticulum, scanty lipids and lysosomes, small mitochondria with lamellar cristae and abundant intracytoplasmic filamentous material. The luteinized cells display a strongly developed tubular agranular endoplasmic reticulum and mitochondria with tubular cristae. These findings are compared with those of previous reports and discussed in relation to the well-known hormonal activity of these tumors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2307
    Keywords: Eosinophilic granuloma ; Frontal lobe ; Histiocytosis-X ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical symptoms, pathological findings and surgical treatment of a case of primary frontal lobe eosinophilic granuloma are presented. Initially a frontal mass was detected that clinically seemed like a low-growth tumor. After operation, the histological, cytochemical and ultrastructural studies showed positive acid phosphatase, α-naftil-esterase, oil-red and PAS reactions of tumoral cells and the presence of rod-shaped bodies in proliferative histiocytes, all which confirmed the pathological diagnosis of eosinophilic granuloma. Other osseous or visceral histiocytosis-X signs were not observed. The patient remains asymptomatic after a postoperative follow-up of 2 years.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 1-11 
    ISSN: 1432-2307
    Keywords: Soft tissue sarcoma ; Myofibroblasts ; Ultrastructure ; Host response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of 129 soft tissue sarcomas was examined ultrastructurally to determine in which neoplasms and to what extent myofibroblasts could be demonstrated. Twenty cases of fibromatosis and fasciitis served as controls. Myofibroblasts were identified in all 30 cases of malignant fibrous histiocytoma and all 4 cases of well-differentiated sclerosing liposarcoma. Though most numerous in areas of desmoplasia, in no instance did myofibroblasts constitute the dominant cellular constituent of either neoplasm. Myofibroblasts were identified with lesser frequency and in smaller numbers in fibrosarcoma, synovial sarcoma, malignant hemangiopericytoma and neuroblastoma. None were observed in a wide assortment of diverse sarcomas in which desmoplasia was not a feature. In comparison each lesion judged by light microscopy to represent either fibromatosis or fasciitis was composed principally of myofibroblasts. The demonstration of abundant myofibroblasts within a soft tissue lesion which has been subjected to wide sampling strongly suggests a benign proliferative process as opposed to a malignant neoplasm. It is hypothesized that myofibroblasts observed within collagenized regions of soft tissue sarcomas may constitute an expression of host response to neoplasia.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 27-41 
    ISSN: 1432-2307
    Keywords: Chondrosarcoma ; Clear-cell chondrosarcoma ; Glucosaminoglycans ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two cases of clear-cell chondrosarcoma located in the upper end of the right femur of men aged 30 and 40 years are reported. The roentgenologic appearances suggested a chondroblastoma. Both patients are alive, one and four years after surgical removal of the tumor. Glucosaminoglycans were studied with cationic dyes at different pH, with and without pretreatment with testicular hyaluronidase, and with the Scott technique at the light-microscopic level. Ultrastructurally, the glucosaminoglycans were studied with the high iron diamine and dialyzed iron techniques and glycogen with the PATCH-method. Light-microscopically, the tumors were characterized by clear vacuolated cells with distinct cytoplasm boundaries and scattered multinucleated giant cells of osteoclast type. Histochemical studies at the light-microscopic level indicate the presence of chondroitin 4- and 6-sulphate but no keratosulphate. Ultrastructurally, the predominant clear-cells showed features characteristic for chondroblasts. The cytoplasm showed areas lacking organelles and containing a low-density, finely granular matrix. These areas are considered to correspond to the clear cytoplasmic vacuoles seen under the light microscope. Most of the organelles were seen in the perinuclear region. The irregular tumor cells formed delicate protruding cytoplasmic extensions, which delineated intercellular spaces appearing as vacuoles under the light microscope. The benign multinucleated giant cells had an ultrastructural appearance typical of osteoclasts. Histochemical analysis at the electron-microscopic level showed the presence of sulphated glucosaminoglycans in the intercellular matrix and in association with the cytoplasmic membrane. Glycogen and non-sulphated acid glucosaminoglycans were found within the cytoplasm of the clear-cells.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2307
    Keywords: Congenital Nephrotic Syndrome of Finnish type ; Histochemical ; Placentomegaly ; Trophoblast basement membrane alteration ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the morphological aspects of a thirty-six week gestational age placenta in the Congenital Nephrotic Syndrome of Finnish type. The study, conducted with histological, histochemical, morphometric and ultrastructural methods, demonstrates the presence of primary disorders of placentation consisting of persistent embryonic villi, arrested ramification and chorionangiomatosis. The villous development is compatible with the first-second trimester of pregnancy. Vasculo-syncytial membranes are quantitatively increased. Histochemical findings document placental immaturity further: Perls' reaction was positive for the trophoblast basement membrane (this is normally not observed beyond the second trimester), Alcian Blue positivity at pH 1 was also evident and was observed in three month gestational age placentae and in controls. Periodic Acid Silver Methenamine and Thioaldehyde Fuchsin documented abnormal thickenings of the trophoblast basement membrane. Electron microscopic observation reveals that the trophoblast basement membrane is thickened. Osmiophilic bodies are distributed throughout the trophoblast basement membrane and also within the basement membrane like material. Abundant microfibrils are present in the villous stroma. Lamination of basement membrane like material is observed in a subendothelial position. On the basis of their findings and in conjunction with the data in the literature regarding biochemical alterations of renal glomerular basement membranes in Congenital Nephrotic Syndrome Finnish type, the Authors suggest that a primitive membranopathy forms the basis for this pathological condition.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 59-77 
    ISSN: 1432-2307
    Keywords: Ethanol ; Myocardium ; Ultrastructure ; Morphometry ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar rats were fed with ethanol for 33 weeks. Ethanol was administered in a liquid diet containing 33% of the calories as ethanol. In the control group ethanol was isocalorically replaced by glucose. Light and electron microscopic investigation of the hearts did not indicate significant structural abnormalities, in contrast to the results of some other groups. Nevertheless, morphometric analysis revealed considerable quantitative changes. The number of mitochondria was remarkably reduced and the volume of an average single mitochondrion nearly doubled, whereas the volume fractions of mitochondria and myofibrils were unaltered. The analysis of the mitochondrial subcompartments indicated a slight decrease of the surface area of inner mitochondrial membranes per unit volume of mitochondria and a slight increase of the volume fraction of the mitochondrial matrix space. Myocardial cell hypertrophy or atrophy were not observed. We believe that the mitochondrial changes are the expression of an impaired biogenesis of these organelles. The increased number of capillaries in the ethanol-fed group is possibly caused by functional ethanol effects which may be partly similar to effects of chronic hypoxia. Ethanol- or acetaldehyde-induced damage of heart mitochondria may play an important role in the pathogenesis of alcoholic cardiomyopathy.
    Type of Medium: Electronic Resource
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 103-117 
    ISSN: 1432-2307
    Keywords: Gonadal dysgenesis ; H-Y antigen ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The gonads of 4 phenotypically female individuals with XY chromosomal constitution and signs of virilisation were examined by light microscopy. Electron microscopic examination was also performed in two cases. Serological analysis of H-Y antigen titer yielded positive results. The matrix of the gonads is shown to be ovarian stroma, in which tubular and follicular structures are embedded. The epithelia of the follicles resemble granulosa cells of the ovary, the tubular epithelia are resemble Sertoli cells. Tubules and follicles both show extensive regressive changes. A varying number of Leyding cells/stroma lutein cells were found in each gonad. The different degree of development of testicular and ovarian structures in the dysgenetic gonads might be explained by a defect of the gonadal specific receptor for the H-Y antigen, this defect varying in time of occurrence, duration and severity.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 287-305 
    ISSN: 1432-2307
    Keywords: Myeloproliferative disease ; Osteomyelofibrosis ; Bone marrow biopsy ; Blast crisis ; Ultrastructure ; Basophilic leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and morphological findings are presented in two patients suffering from myelofibrosis and osteomyelosclerosis which terminated in an acute blastic crisis. Clinical follow-up data and light microscopy of the bone marrow however, revealed a chronic megakaryocytic-granulocytic myelosis (CMGM) with progression into myelofibrosis during the course of disease. In one patient the blastic transformation involved predominantly basophils, and in the other, neutrophils, with an accompanying abnormal proliferation of megakaryocytes in both cases. Electron microscopy of this cell population demonstrated remarkable atypicalities of the neutrophilic, basophilic and megakaryocytic cell lines. These abnormalities consisted of a nuclear-cytoplasmic asynchrony and a partial arrest of maturation, sometimes resulting in bizarre cell forms. Our investigations support the hypothesis of a mixed cellularity type of myelosis with a gradual and insiduous progression into osteomyelofibrosis/-sclerosis and a potential blastic crisis. In the evolution of blastic crisis all cell lines may be transformed, but with predominance of one population — basophils and neutrophils in our two cases — in addition to atypicalities of megakaryocytes.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 307-324 
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Secondary polycythemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and morphological studies including light microscopy, electron microscopy and karyotyping of the bone marrow, were performed on a total of 164 patients with polycythemic conditions. A final diagnosis was obtained from clinical findings and histopathology of plastic embedded core biopsies of the bone marrow including sequential examinations. 51 patients revealed a secondary polycythemia whereas 113 displayed polycythemia vera (P. vera). In this last group 83 cases have persisting P. vera. 30 showed a transgression towards chronic myeloid leukemia with or without accompanying myelofibrosis — osteomyelosclerosis (so called chronic megakaryocytic-granulocytic myelosis — CMGM). The histopathology of the bone marrow in P. vera revealed consistent alterations which are useful in distinguishing this disorder from secondary polycythemia (SP) and CMGM: depletion of iron storage, increased neutrophilic granulopoiesis but no gross atypia in maturation, polymorphism of megakaryocytes with conspicuous giant forms and dilatation and increased branchings of venous sinusoids. Electron microscopic findings were in agreement and showed further abnormalities of cytological maturation in the erythrocytic and granulocytic lineage. Cytogenetic studies in 27 non-treated patients with P. vera revealed the Philadelphia chromosomes in 2 cases, whereas in SP only minor chromosomal anomalies have been encountered in a few patients. It is concluded that histopathology of trephine biopsies of the bone marrow is an invaluable aid to establish a correct diagnosis, differentiating P. vera from the other potentially polycythemic disorders and helping to detect a possible progression towards leukemia at an early stage. Cytogenetic investigations may show early structural and numerical abnormalities of the karyotype and possibly precede a presumptive transgression towards myeloid leukemia (CMGM). A simultaneously performed histological and chromosomal examination of bone marrow samples is therefore desirable in each case of a polycythemic condition.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 325-341 
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Myeloid leukemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Of 113 Patients with polycythemia vera (P. vera) who had been followed for the last 8 years, 30 cases (27%) developed myeloid leukemia with fibrosis of the bone marrow. Core biopsies of the bone marrow including sequential examinations in several cases revealed neoplastic proliferation of neutrophil granulopoiesis and an atypical megakaryopoiesis with accompanying fibrosis of varying degrees. These alterations were consistent with a subtype of chronic myeloid leukemia — the so called chronic megakaryocytic-granulocytic myelosis (CMGM) — and correspond to (agnogenic) myeloid metaplasia with osteomyelofibrosis/-sclerosis. 5 of those 30 patients showed spontaneous transgression into myeloid leukemia, none of them had received any ionizing radiation or cytostatic therapy. A blast crisis or so called acute leukemia in P. vera was seen only in one patient who was treated by an overdose of radioactive phosphorus and later evolved into osteomyelosclerosis with blastic transformation. These findings of a chronic leukemia or CMGM arising from P. vera was further confirmed by atypia of ultrastructure and particularly by our cytogenetic evaluation. Chromosomal studies showed a Ph′-chromosome to be present in 5 of 8 patients with CMGM and myelofibrosis. Clinical and statistical evaluation of survival times showed a median survival expectation of all P. vera patients of 15 years. Life expectancy of the patients who still displayed P. vera was more favorable than those cases with transformation into CMGM, disregarding any therapy. Transformation of P. vera into CMGM occurred about 8 years after the onset of disease and following transgression into leukemia, half of these patients were dead after 2.5 years. Our results demonstrate that P. vera represents a “panmyelosis” with an inherent malignant nature, or a neoplastic proliferation of all three cell lines. This concept is supported by several facts: atypia of cytological differentiation as observed by light- and electron microscopy of the bone marrow, chromosomal anomalies with aneuploidy and an infrequent Ph'-marker, spontaneous transgression into chronic myeloid leukemia or its subtype CMGM without relevant therapy and a clonal evolution as shown by enzymatic studies reported in the literature.
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  • 15
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; 5,7-Dihydroxytryptamine ; 5-HT ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5,7-Dihydroxytryptamine (5,7-DHT) or the vehicle was administered once into both lateral ventricles of the rat. Desmethylimipramine (DMI) was administered IP prior to the intraventricular injection of 5,7-DHT to prevent the destruction of norepinephrine (NE) terminals. Following recovery from surgery, ethanol (5 g/kg, PO) or isocaloric sucrose was given daily for 25 days. Tests at 5-day intervals showed that chronic ethanol treatment produced tolerance to the motor impairment on the moving belt test and to hypothermic effects of ethanol. The 5,7-DHT treatment did not alter either the motor impairment or hypothermia produced by the initial dose of ethanol. However, 5,7-DHT treatment produced a 75% depletion of brain serotonin (5-HT) without altering NE concentration and retarded the development of tolerance to ethanol in both measurements. This study with a specific central depletor of 5-HT, without alteration in NE concentration, extends and supports our hypothesis that brain 5-HT modulates the development of tolerance to ethanol.
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  • 16
    ISSN: 1432-2072
    Keywords: Continuous amphetamine ; Hallucinogens ; Limb flicks ; Shakes ; Grooming ; Model psychosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats injected with LSD or mescaline show the behavioral syndrome which has been previously reported following injections of hallucinogens in higher mammals: limb flicks and whole body shakes. Although these behaviors are not elicited by acute injections of amphetamine, they are present in rats which have been pretreated for 108 h with a slow-release amphetamine pellet, given a 12h rest period, and then injected with d-amphetamine. Such pellet-pretreated animals also groom their body surface excessively. We propose that this novel syndrome which follows continuous amphetamine administration can serve as an animal model of the type of amphetamine psychosis that is produced by a similar drug regimen in humans.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 68 (1980), S. 257-259 
    ISSN: 1432-2072
    Keywords: Metrazol ; Conditioned taste aversion ; Rat ; Two bottle test preference ; Saccharin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Employing a two bottle drinking procedure where an animal's preference is measured between plain water and a novel fluid, it was found that the convulsant drug Metrazol produced a conditioned taste aversion to saccharin. This finding is contrary to that of previous reports and highlights the sensitivity of the two bottle method in detecting a taste aversion.
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  • 18
    ISSN: 1432-2072
    Keywords: Diazepam ; Naloxone ; Behavioral inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of naloxone on diazepam-induced release of behavior in aversive situations were investigated in rats. Naloxone (0.5 and 1 mg/kg-1) suppressed diazepam-induced eating in an unfamiliar situation and reduced (1 mg/kg-1) spontaneous food intake. Naloxone (1 mg/kg-1) canceled the increased lever pressing produced by diazepam in a conflict procedure in which one electric shock was delivered at each seventh press. Naloxone (1 mg/kg-1) failed to reverse the enhanced responding for food induced by diazepam in the presence of a signal previously paired with electric foot shocks. In this situation, naloxone alone reinforced the behavioral suppression. These results suggest that transmission mediated by opiate peptides may be involved in only some ‘disinhibitory’ effects of benzodiazepines. In addition, such a peptidergic transmission may play a role in the control of stress-induced behavioral suppression.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 69 (1980), S. 183-185 
    ISSN: 1432-2072
    Keywords: DPH ; Genral activity ; Stereotypy ; Supersensitivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Animals were administered increasing doses of diphenylhydantoin (DPH) for 20 days. During withdrawal they were observed in an open field. The results suggest that chronic DPH administration leads to a central supersensitivity phenomenon. Possible interference of DPH with dopaminergic systems was discussed.
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  • 20
    ISSN: 1432-2072
    Keywords: Rating scales ; Photocell activity cages ; Measurement ; Stereotypy ; d-Amphetamine ; Apomorphine ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0–15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0–5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or stereotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 386 (1980), S. 221-230 
    ISSN: 1432-2013
    Keywords: Optokinetic system ; Pretectum ; Visual vestibular convergence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1) The responses of single units in the pretectum (Pt) and in the n. reticularis tegmenti pontis (NRTP) to constant velocity horizontal rotation (0.25–60 deg/s) of a large-field visual pattern were studied in immobilized, non-anesthetized DA-HAN rats. In addition, responses of Pt and NRTP neurons to pure vestibular stimuli (rotation in the dark) were studied. 2) Pt neurons showed seven response types to optokinetic stimulation (Table 1). The most frequent response (48%) consisted of a very rapid increase in firing to steady state on temporonasal motion stimulation of the contralateral eye; nasotemporal stimuli yielded no change in resting rate as did stimulation of the ipsilateral eye. The response maximum occurred at a retinal slip velocity of 1 deg/s. None of the Pt units tested responded to pure vestibular stimuli. 3) NRTP neurons — as Pt units — most frequently (43%) increased their discharge rate on temporonasal stimulation of the contralateral eye and maintained a constant resting rate during nasotemporal motion. Peak response amplitudes also occurred with retinal slip velocities of 1 deg/s. Contrary to the fast time-to-peak of the responses of Pt neurons NRTP units showed a slow rise in frequency of firing to peak response levels. 4) NRTP neurons responded to pure vestibular stimuli (horizontal angular acceleration in the dark). The vestibular responses were synergistic with those evoked in the same neurons by optokinetic stimuli. Thus, the most frequently encountered type of optokinetic response (s. above) showed a type II vestibular response. 5) Comparison of OKN and Vn optokinetic responses with those of Pt and NRTP suggests that the unidirectional-selective Pt and NRTP neurons are important links in the central optokinetic path. In addition, the NRTP may represent the site at which the retinal slip signal and the eye velocity signal converge. This convergence has been postulated in models of the system [12].
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  • 22
    ISSN: 1432-2013
    Keywords: Rat ; Micropuncture ; Tubuloglomerular feedback ; DOCA-salt treatment ; Extracellular volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experiments were performed in anesthetized rats to investigate the time course of the adaptive changes in tubuloglomerular feedback reactivity and juxtaglomerular renin activity induced by DOCA and NaCl loading (isotonic saline as drinking fluid plus daily injections of 25 mg/kg DOCA). In these DOCA escaped rats we studied further the effect of acute volume depletion and repletion on the magnitude of feedback responses. A significant reduction of feedback reactivity was found on the fifth day after starting the DOCA-salt treatment with maximum depression being established after two weeks. In contrast, significant reduction of juxtaglomerular renin content required 10 days and maximum depression three weeks of DOCA-salt administration. In DOCA-salt treated animals with severely curtailed feedback responses acute volume depletion was induced by a single injection of furosemide (10 mg/kg) leading to an excretion of 0.49 ±0.17 mEq sodium and a mean decrease of body weight of 2.17±0.22% over a period of 60–70 min. Mean feedback response (expressed as percent change of early proximal flow rate caused by elevating loop of Henle flow rate from zero to 40 nl/min) was −43.9 ±4.0%, significantly greater than in the pre-depletion phase and indistinguishable from responses seen in normal control rats. Repletion of extracellular volume by infusing HCO3-Ringer solution over 20 min induced a reduction in feedback responsivity to −12.0±2.9%. Plasma and juxtaglomerular renin concentration increased with volume depletion and decreased with volume repletion, but remained considerably lower than observed in normal control rats. Our results suggest that the tubuloglomerular feedback system responds to acute alterations in extracellular volume with rapid adaptations in its reactivity which is consistent with its role in the control of sodium excretion.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 387 (1980), S. 67-68 
    ISSN: 1432-2013
    Keywords: Hepatic vein ; Catheterization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A procedure for catheterization of a right hepatic vein is described in the rat. The procedure is based on the observation that, when the posterior half of the body is bent to the left, a right hepatic vein is aligned with the axis of anterior vena cava and posterior vena cava. A catheter, inserted in the right jugular vein and fitted with a rectilinear mandrel, is guided into the right auricle, the suprahepatic segment of posterior vena cava and a right hepatic vein. Successful catheterization of a right hepatic vein has been obtained in 47 out of 50 animals in which the procedure has been performed.
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  • 24
    ISSN: 1432-2013
    Keywords: Secretin ; Vasoactive intestinal peptide ; Glucagon ; Isoproterenol ; Adenylate cyclase ; Heart ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Membrane adenylate cyclase from rat heart was activated by the two gut peptides secretin and vasoactive intestinal peptide (VIP), glucagon, and the β-adrenergic drug isoproterenol, in the presence of guanosine 5′-triphosphate (GTP). With all the stimuli tested, the optimal magnesium concentration was 5 mM, i.e. in excess over the 0.5 mM ATP substrate concentration and 0.01 mM GTP used as cofactor. Under these conditions, half-maximal adenylate cyclase activation with glucagon, secretin, and VIP was achieved at concentrations of 0.5, 0.5 and 1.0 μM, respectively. Data obtained with the secretin (7–27) fragment, a secretin antagonist, indicate that secretin and VIP acted on the same binding sites, which differed from glucagon binding sites. Structural requirements for secretin activation of cardiac adenylate cyclase were evaluated by comparing the potency and efficacy of parent peptides and synthetic analogs. The gastric inhibitory peptide GIP was inactive. When using 13 mono-or bi-substituted analogs, it appeared that amino acids in positions 1, 2, 3, 4 and 6 were of major importance while those in position 5 and 11 played a relatively minor role.
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  • 25
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    Pflügers Archiv 385 (1980), S. 161-165 
    ISSN: 1432-2013
    Keywords: Glomerular filtration rate ; Unilateral nephrectomy ; Compensatory hypertrophy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in the glomerular filtration rate (GFR) were studied in rats, 4 h to 4 weeks after unilateral nephrectomy (NX). The GFR was determined with a technique using51Cr-EDTA and a single timed blood sample. The GFR determined in this way corresponded with the GFR calculated by two compartment analysis and with the plasma levels of creatinine and urea. Increases in the GFR, compared with half the GFR of sham operated rats, were observed as early as 4 h after NX. This increase was entirely due to an increase in the GFR per gram of kidney, since no increase in kidney weight was observed at that time. After the initial increase, the GFR remained at that level during the first 48 h after NX. At 48 h a significant increase in kidney weight per 100 g body weight had taken place. The longterm changes in the GFR amounted to an increase of about 80% of that of sham operated rats after 3–4 weeks. After 4 weeks, the increase in the GFR of the remaining kidney was due to an increase in kidney weight of 35% as well as an increase in the GFR per gram of kidney of 20%. These data indicate that the increase in the GFR of the remaining kidney after unilateral NX occurs rapidly and is independent of an increase in kidney weight. Compensatory hypertrophy develops at a later stage and helps to maintain the increased function of the single remaining kidney.
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  • 26
    ISSN: 1432-2013
    Keywords: Rat ; Renal hypertension ; Plasma renin activity ; Water intake ; Declipping ; Reclipping ; Converting enzyme inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Application of a renal artery clip in rats with an undisturbed contralateral kidney caused a sustained increase in blood pressure and a transient rise of plasma renin activity and water intake. The response of blood pressure, plasma renin activity and water intake was augmented after reapplication of the clip to normotensive declipped rats (renal hypertensive rats, from which the clip had been removed 24 h before the reapplication). The time-course of the changes of blood pressure, plasma renin activity and water intake were similar after the initial application as after reapplication of the clip. Administration of an inhibitor (SQ 14.225) of the converting enzyme abolished the increase in blood pressure and water intake after reapplication of the clip. These data indicate a critical role of renin in the rise of blood pressure and water intake after initial application of a renal artery clip as well as after reapplication of the clip to declipped rats.
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  • 27
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    Pflügers Archiv 387 (1980), S. 121-126 
    ISSN: 1432-2013
    Keywords: Local tissuepO2 ; Hypoglycemia ; Brain cortex ; ECoG ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oxygen supply of the brain cortex together with changes in the electrocorticogram (ECoG) were investigated during and after insulin induced hypoglycemia in 13 anaesthetized rats. Local oxygen partial pressures (pO2) on the parietal cortex were continuously measured with a multiwire surface electrode of the Clark type. During early hypoglycemia with a mean arterial glucose concentration [G]a of 2.81 (SD ±0.40) mmol/l, the local tissuepO2 did not change significantly as compared to thepO2 values recorded during the control period with a normal [G]a of 4.51 (SD±0.70) mmol/l. During severe hypoglycemia at a [G]a of 1.39 (SD±0.2) mmol/l,pO2 began to increase continuously on all 104 measuring sites, independently of changes in arterial blood pressure and ECoG. During a period of 7–18 min of isoelectricity, tissuepO2 remained elevated so long as blood pressure did not decrease. After injection of a 25% glucose solution,pO2 gradually decreased to control values within 30–60 min in most experiments. We conclude from these results that oxygen supply is generally improved during severe hypoglycemia. We assume that the increase in tissuepO2 is mainly caused by an increase in microflow. Thus, the neuronal damage occurring after severe hypoglycemia, as reported in literature, cannot primarily be caused by an oxygen deficiency.
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  • 28
    ISSN: 1432-2048
    Keywords: Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The growth of white clover (Trifolium repens L.) is severely inhibited by boron starvation, but a foliar treatment with boric acid can transitorily alleviate the deficiency symptoms. The 10B(n ,α)7 Li nuclear reaction has been used to study boron transport in the plant after foliar application. More than 98% of the boron supplied remained at the point where it was applied to the leaves, and less than 2% was useful to the growth of the treated plant. This small “efficient” portion of boron was quite mobile. It was distributed to the different parts of the plant, then was transferred from the oldest parts to the newly formed leaves. Physiological and agronomical implications of these data are discussed.
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  • 29
    ISSN: 1432-2307
    Keywords: Cortisol ; Myocardium ; Ultrastructure ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar rats were treated with high cortisol doses for 1 week. The dose administered daily was 15 mg per animal in group 1 (7 animals) and 30 mg in group 2 (7 animals). 7 rats served as control group. After cortisol treatment the body weights decreased due to skeletal muscle catabolism and the heart weights increased. Morphometric analysis of the left ventricular posterior papillary muscles gave evidence that the increased heart weights resulted from an increased number of mitochondria and an increased volume of the cytoplasm, whereas the myofibrillar mass was not affected. The surface area of inner mitochondrial membranes (+cristae mitochondriales) per myofibrillar unit volume increased from 15.7 μ2/μ3 to 21.3 μ2/μ3 in group 1 and 21.4 μ2/μ3 in group 2. Ultrastructural changes indicating myocardial cell damage were absent. Similar quantitative results have been reported to occur in the early phase of cardiac overload. For elucidating the hemodynamic effects of glucocorticoid a second experiment was performed: 7 Wistar rats were treated with cortisol in the same way as group 1, 7 others of the same body weight served as control. The systolic arterial pressure was significantly elevated in the cortisol group. Though myocardial tissue is known to be able to accumulate large quantities of glucocorticoids our results indicate that the application of high cortisol doses for a short time does not produce myocardial cell damage and does not suppress the myocardial adaption to the glucocorticoid-induced hypertension, i.e. hypertrophy. On the contrary, it seems to be possible that the adaption process is itself facilitated or accelerated by the presence of high cortisol concentrations in the heart. This thesis is supported by the considerably higher relative heart weights in the cortisol groups and is in agreement with observations reported by other authors.
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  • 30
    ISSN: 1432-2307
    Keywords: Tumor promotion ; Tumor initiation ; DMBA ; TPA ; Two-stage carcinogenesis experiment ; Carcinogenesis ; Cocarcinogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In contrast to a previous report by Shubik, the validity of the 2-stage skin carcinogenesis experiment was demonstrated in the rat. The modified experiment was carried out in female Sprague-Dawley rats using intragastrically administered DMBA as a carcinogen and the topically applied phorbol ester TPA as a promoter. Seven groups of animals were used. Two groups were treated with TPA only, two groups were initiated only with DMBA, two further groups were both initiated and promoted, and one group served as a control. Each of the initiated/promoted groups or only initiated or promoted groups contained one sub-group in which the animals had been bilaterally ovarectomized prior to the experiment. Hyperplasia of the dorsal epidermis occurred only in the promoted and in the initiated/promoted groups. Tumors of the back skin were observed exclusively after initiation/promotion. Ovarectomy — leading to a prolonged survival time of the animals — seems to be crucial for the manifestation of malignant skin tumors. Initiation/promotion also gives rise to tumors of the forestomach, the small intestine, the liver and the colon. Tumors in other organs (especially in the mammary gland and the Zymbal gland) were also be observed after initiation alone.
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  • 31
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    Virchows Archiv 386 (1980), S. 331-341 
    ISSN: 1432-2307
    Keywords: Fluorocarbon ; Extracorporeal circulation (EEC) ; Pulmonary ; systemic embolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After intravenous injection of 0.1 ml Fluorocarbon (FC) into the caudal vein of rats clear droplets which are reminiscent of gas emboli appear in the pulmonary and cerebral arteries. These droplets cannot be stained with Azan, haematoxylin-eosin, Nile blue sulfate, Sudan black B, and Sudan III in Paraplast embedded or frozen sections. Gas chromatography of affected lung tissue reveals a high concentration of FC. The clear droplets are the histological correlates of FC emboli which lead to haemorrhagic lung infarction and ischaemic brain infarcts. After intralienal injection FC induces haemorrhagic infarcts of the spleen near the injection site and massive embolization of the intrahepatic portal veins with consequent liver cell necrosis. FC droplets are phagocytosed by hepatic sinusoidal lining cells. Due to the absence of a specific method for identifying FC embolization of renal vessies is difficult to assess.
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  • 32
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    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 265-270 
    ISSN: 1432-1912
    Keywords: Phyllomedusa sauvagei ; Sauvagine ; Blood pressure ; Diuresis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The occurrence of sauvagine, a new polypeptide from amphibian skin, and its actions on rat blood pressure and diuresis were studied. 2. Sauvagine was found to be present in the skin of all the 10 Phyllomedusa species so far studied, amounts ranging from a few micrograms to 240 μg per g fresh skin. 3. The polypeptide displayed in the rat an intense, long-lasting hypotensive action accompanied by tachycardia. Hypotension was not modified by either atropine or propranolol, excluding the participation of the autonomic nervous system in its production. Tachycardia, on the contrary, was partially inhibited by propranolol. 4. Hypotension is probably the main cause of the intense antidiuresis seen in hydrated rats following sauvagine administration. Reduction in urina volume was accompanied by a decrease in GFR and an increase in tubular Na+ reabsorption.
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  • 33
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    Journal of molecular medicine 58 (1980), S. 501-510 
    ISSN: 1432-1440
    Keywords: Primärer Hyperparathyreoidismus, klinische und klinisch-chemische Befunde ; Akuter Hyperparathyreoidismus ; Ultrastruktur ; Hypercalciämie ; Parathormonspiegel ; Primary hyperparathyroidism, clinical and laboratory findings ; Acute hyperparathyroidism ; Ultrastructure ; Hypercalcemia ; Parathormone, blood level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In a series of 6 patients out of 47 cases with extrarenal hyperparathyroidism we investigated the clinical, laboratory and ultrastructural peculiarities of acute hyperparathyroidism. It was found that there are characteristic differences between both entities which, however, are fluid. Clinically more severe were neuromuscular psychiatric and mental signs. In the laboratory parameters PTH determined by radio-immunoassay and calcium were higher whereas hemoglobin was lower. The weights of the adenomas did not differ in both groups and this was also true for light microscopy findings. Electron microscopy revealed accelerated hormone extrusion and autodigestion of retrieved membrane material in the cases of acute hyperparathyroidism similar to characteristics of parathyroid cells stimulated by hypocalcemia in tissue culture.
    Notes: Zusammenfassung Bei 6 Kranken mit akutem Hyperparathyreoidismus werden klinische Befunde, Labordaten und Besonderheiten in der Ultrastruktur der Nebenschilddrüsen den Daten von 47 Kranken mit extrarenalen Hyperparathyreoidismus gegenübergestellt. Typische Unterschiede konnten aufgezeigt werden, die Übergänge sind aber fließend. Beim klinischen Verlauf waren neuromuskuläre Zeichen, psychiatrische und Störungen des Bewußtseins deutlicher in der ersten Gruppe. Beim Vergleich der Labordaten war radioimmunchemisches Parathormon höher in der akuten Gruppe und das Hämoglobin niedriger. Das Gewicht der Adenome und die lichtmikroskopischen Befunde waren nicht unterschiedlich in beiden Gruppen. Die elektronenmikroskopischen Studien des Adenomgewebes zeigten eine erhöhte Hormonausschüttung mit einer deutlichen Beschleunigung der Autodigestion von Membranmaterial. Diese Veränderungen entsprechen etwa denen, wie sie an Nebenschilddrüsengewebe in der Gewebekultur nach Stimulation durch Hypocalciämie gefunden werden.
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  • 34
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    Journal of cancer research and clinical oncology 96 (1980), S. 281-285 
    ISSN: 1432-1335
    Keywords: Carcinogenesis ; Thyroid gland ; Rat ; NMU ; MTU
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seventy-five female Wistar rats of 150 g each were given 3×40 mg/kg body weight nitrosomethylurea (NMU) and 4 weeks later until death (in the 9th–60th week) methylthiouracil (MTU), as a 0.1% solution in their drinking water. After 2 months, in the almost colloid-less thyroid gland individual foci appeared which consisted of sometimes colloid containing follicles with increased cytoplasmic and nuclear basophilia; they increased in number during the subsequent weeks and finally resulted in nodes with different morphologic structures. From the 16th week on there were tumors infiltrating the capsule, and after the 24th week there were angioinvasive carcinomas. Thirteen rats had developed lung metastasization after the 30th week. Cytology could only distinguish between the follicular carcinomas of low differentiation and the follicular adenomas. If these findings are applied to human pathology, one would have to reckon with adenomas which can develop their malignant characteristics without necessarily changing their histologic and cytologic appearance.
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  • 35
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    Experimental brain research 39 (1980), S. 121-124 
    ISSN: 1432-1106
    Keywords: Amygdala ; Medial preoptic nucleus ; Median eminence ; Rat ; Synaptic plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Stimulation-dependent changes in synaptic effects were observed in medial preoptic nucleus neurones during stimulation of the amygdala or pyriform cortex in anaesthetized female rats. The changes occurred after 35–240 triple pulse stimuli repeated at 0.89 Hz. Median eminence stimulation did not produce any synaptic change. These data show the existence of synaptic plasticity in the neural pathway from the amygdala and pyriform cortex to the medial preoptic nucleus.
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  • 36
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    Experimental brain research 39 (1980), S. 241-248 
    ISSN: 1432-1106
    Keywords: Olfactory peduncle neurons ; Axonal branching ; Supernormal period ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological methods were employed to study the axonal properties of the neurons of anterior olfactory nucleus (AON), transition zone (TZ), and rostral prepyriform cortex (RPPC) and their projections towards the ipsilateral and contralateral olfactory bulb (IOB, COB) in the rat. Of 91 antidromically driven cells, 39 (43%) and 32 (35%) responded to IOB and COB stimulation, respectively; 20 (22%) were discharged from both bulbs. Collision tests performed on the latter group indicated that these neurons have a short main axon which divides near the soma, projecting one branch to the COB and a thinner one toward the IOB. Mean conduction velocities of axons projecting to the IOB and the COB were 0.4 m/s and 0.7 m/s, respectively, the faster conducting axons having shorter refractory periods. Of the 38 neurons tested, 92% showed decreases in threshold and latency (up to 20% of control antidromic latency) after a test volley that was preceded by a conditioning pulse at intervals of 20–215 ms. Latency decreases were greater for slowly conducting axons than for the faster ones. These after-effects of impulse activity in OB afferent axons were attributed to the presence of a supernormal period of increased conduction velocity and excitability similar to that found in the olfactory nerve (Bliss and Rosenberg, 1974).
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  • 37
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    Experimental brain research 40 (1980), S. 79-87 
    ISSN: 1432-1106
    Keywords: Spinal tract neuron ; Hypothalamus ; HRP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution and number of hypothalamospinal tract (HST) neurons were studied following injections of horseradish peroxidase (HRP) at various levels of the rat spinal cord. The hypothalamus was divided into four areas and one nucleus, that is, the dorsal (DHA), posterior (PHA), medial (MHA) and lateral (LHA) hypothalamic areas and the paraventricular nucleus (PVN). The total numbers of HST neurons labeled with HRP varied according to the injection levels: 6,160 (C2 injections), 3,808 (T8), 1,961 (L1), 919 (L7) and 13 (S4). With C2 injections LHA contained 3,464 neurons, which accounted for 56% of the full number of HST neurons; similarly, PVN, 1,114 (18%); MHA, 865 (14%); DHA and PHA, 817 (12%). With L7 injections, LHA contained 444 labeled neurons, which accounted for 48% of the total; PVN, 327 (36%); MHA, 71 (8%); DHA with PHA, 77 (8%). As for the rostrocaudal distribution of labeled neurons, there was only a slight difference between the C2 and L6 injections in LHA, but no difference was noticed in PVN, DHA nor PHA. The present findings suggest that 70% of HST neurons may project to the cervical and thoracic cords. Although the number of labeled HST neurons decreased as the injection sites were placed caudally, no clearcut topographical arrangement was recognized in terms of the spinal projection levels.
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  • 38
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    Calcified tissue international 31 (1980), S. 93-108 
    ISSN: 1432-0827
    Keywords: Calculus ; Ultrastructure ; Apatite ; Transmission ; Scanning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Using transmission and scanning electron microscopy, we have studied the ultrastructure of a number of urinary calculi, mainly composed of calcium phosphate. Three fundamental kinds of calcium phosphates were detected: nonstoichiometric carbonate apatite, nonhexagonal octacalcium phosphate, and calcium-magnesium whitlockite. The influence that the organic matter, substitutions in the phosphate lattice of CO3 and Mg, and apatitic stoichiometry have on the ultrastructure of the calcium phosphate calculi has been detailed. An originating apatitic unity named U2 is assumed to be the responsible for all the different structures of calcium apatites appearing in renal calculi. On the basis of our observations, a mechanism whereby apatites grow is postulated; magnesium functions as an inhibitor for the growing mechanism.
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  • 39
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    Calcified tissue international 32 (1980), S. 63-68 
    ISSN: 1432-0827
    Keywords: Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
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  • 40
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    Calcified tissue international 32 (1980), S. 113-122 
    ISSN: 1432-0827
    Keywords: Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
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  • 41
    ISSN: 1432-0827
    Keywords: Rat ; Hypophysectomy ; Dietary phosphorus deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
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  • 42
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    Archives of gynecology and obstetrics 230 (1980), S. 123-135 
    ISSN: 1432-0711
    Keywords: Clip ; Bleier-Clip ; Tube ; Histologie ; Sterilisation ; Ultrastruktur ; Clip ; Bleier clip ; Fallopian tube ; Histology ; Sterilization ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A bilateral salpingectomy was performed at the time of vaginal hysterectomy in a pregnant patient sterilized 20 months earlier by application of Bleier clips to the fallopian tubes. Clip application to the left tube had been incomplete. Undisturbed tissue (left tube) and clipped tissue (right tube) were examined and compared by light and scanning electron microscopy. The segment of tube fully grasped by the clip had a completely detached lining epithelium with coarse and flattened mucosa, a loose stroma, and disorganized muscular bundles. The left tubal mucosa was normal, whereas the right tube was stenosed at the site of clip placement, with rigid walls and a 0.175 mm luminal diameter. With progressively greater stenosis toward the clip site, mucosal destruction increased. Polypoidal mucosal folds were seen, as well as fibrous adhesions between mucosal folds. These observations indicate that tissue damage is extensive enough after clip application to require excision of the damaged segment of tube and microsurgical re-anastomosis for reversal of sterilization.
    Notes: Zusammenfassung Das Untersuchungsgut, über welches hier eingehend berichtet wird, stammt von einer 37jährigen Schwangeren (8. Woche), bei welcher 20 Monate zuvor eine Sterilisation mit Bleier-Clips versucht worden war. Es ergab sich eine Indikation zur Hysterektomie mit bilateraler Salpingektomie, was uns erlaubte, die gewebliche Reaktion einer Tube, an der ein Bleier-Clip korrekt saß, mit der an der kontralateralen Tube, über welche die Schwangerschaft eingetreten war, zu vergleichen. Die Präparate wurden rasterelektronenmikroskopisch und anschließend an identischen Stellen desselben Blocks lichtmikroskopisch untersucht („post-scanning histology“). In der voll gefaßten rechten Tube war das luminale Epithel streckenweise von der Unterlage abgehoben, das Faltenrelief der Mucosa distal und proximal der Clipmarke vergröbert oder abgeflacht, das subepitheliale Bindegewebe aufgelockert und die Bündel der Muscularis auseinandergedrängt. Die nur partiell mitgefaßte und daher noch ausreichend durchgängige linke Tube war zwar stenosiert, jedoch abgesehen von Schwangerschaftszeichen ohne markante Veränderung des Epithels. In der durch der korrekt sitzenden Clip verschlossenen rechten Tube verengte sich die Stenose der Clipmarke trichterförmig von proximal wie von distal, ein solider Epithelstrang war lichtmikroskopisch jedoch durchgehend nachzuweisen. Schleimhautmikropolypen und narbige Überbrückungen des Faltenreliefs in unmittelbarer Nachbarschaft des korrekt sitzenden Clips veranschaulichen, ebenso wie die narbigen Veränderungen der Tubenwand, daß eine funktionsfähige Wiederherstellung der Tubenkontinenz nach Entfernung eines zur temporären Sterilisierung applizierten Bleier-Clip kaum anders als durch eine mikrochirurgische Reanastomosierung nach Resektion der narbigen Stenose erwartet werden kann.
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  • 43
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    Archives of toxicology 43 (1980), S. 257-262 
    ISSN: 1432-0738
    Keywords: Bromobenzene ; Cytochrome P-450 ; Cytochrome reductase ; Glucuronyltransferase ; Lipoperoxidation ; Liver ; Mixed-function oxidase ; Peroxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In acute oral studies, the effect of bromobenzene on hepatic microsomal enzymes was investigated. Neither glucuronyltransferases nor cytochrome c reductase showed significant changes. Most of the mixed-function oxidases studied were inhibited with the exception of ketamine-N-demethylase. The data indicate that bromobenzene or its epoxide acts on cytochrome P-450 but not on all cytochrome P-450 species, and does not affect the reductase and the glucuronyltransferases. Microsomal lipoperoxidation and microsomal H2O2 formation were increased.
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  • 44
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    Calcified tissue international 30 (1980), S. 27-34 
    ISSN: 1432-0827
    Keywords: Ultrastructure ; Calcium ; Cartilage ; Vesicles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The potassium pyroantimonate technique was utilized for the selective subcellular localization of calcium in the mandibular condylar cartilage of 1-day-old rats. Electron dense calcium pyroantimonate precipitates were localized principally in mitochondria and at the cell membrane of the chondrocytes. In addition, small intracellular vesicles 0.1–0.2µm in diameter were observed in proximity to the cell membrane of chondrocytes of the mid-hypertrophic zone. The results suggest that these vesicles were being extruded from the cell into the extracellular matrix. Energy-dispersive analysis by X-rays confirmed that calcium is the principal cation of the electron-dense precipitates.
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  • 45
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    Anatomy and embryology 160 (1980), S. 239-252 
    ISSN: 1432-0568
    Keywords: Liver ; Innervation ; Adrenergic nerves ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The adrenergic innervation of rat and guinea pig liver is investigated using the glyoxylic-acid — paraformaldehyde method for fluorescent microscopical demonstration of adrenergic nerves and electron microscopy. The nerve distribution in the parenchyma of both animals is compared. The distribution of the liver nerves as detected with fluorescence microscopy is confirmed electron microscopically. The two species exhibit fundamental differences in their liver innervation: (1) In the guinea pig, a rich innervation is found in the trias as well as in the parenchyma. Many nerves traverse the entire liver lobules and may end near the central vein. The guinea pig hepatocyte innervation seems to be uniformly adrenergic. Electron microscopy shows that the varicosities of these nerves mostly form close contacts to the hepatocytes but also to other hepatic intralobular cells. (2) In the rat, the liver nerves are as a rule restricted to the triads, running mainly with smooth muscle containing blood vessels. It rarely happens that nerves penetrate into the lobule and come into contact with the peripherally located hepatocytes.
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  • 46
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    Anatomy and embryology 160 (1980), S. 275-284 
    ISSN: 1432-0568
    Keywords: Adenohypophyseal rudiment ; Follicular cells ; Ultrastructure ; Culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epithelial rudiment of 4 day-old quail embryo adenohypophysis, cultivated in vitro under conditions allowing glandular differentiation, displays peripheral cells that progressively acquire follicular cell features. They elongate, develop numerous microvilli, junctional complexes, interlocking membranes and bundles of microfilaments. These follicular-like cells derive from peripheral epithelial cells that, in situ, become glandular. These results show that follicular cells can develop from undifferentiated cells. They undergo this pathway of development, in all likelihood, as a result of perturbations in their microenvironment.
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  • 47
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    Archives of dermatological research 267 (1980), S. 275-282 
    ISSN: 1432-069X
    Keywords: Allergic contact dermatitis ; Epidermal cell changes ; Ultrastructure ; Allergische Kontaktdermatitis ; epidermale Zellveränderungen ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Frühe epidermale Veränderungen bei allergischer Kontaktdermatitis wurden im Elektronenmikroskop untersucht. Gesunde freiwillige Testpersonen wurden mit DNCB sensibilisiert und in der Folge Kontaktreaktionen hervorgerufen. Epidermale Zellveränderungen nach 3 h waren unter anderem: Auftreten kleiner Vakuolen mit oder ohne Membran, stellenweise Erweiterung des Intercellularraums und eine Veränderung des Tonofilaments in kurze, gehäufte Bündel. Nicht sensibilisierte Haut, auf die DNCB appliziert wurde, zeigte auch kleine Vacuolen mit oder ohne Membran. Monocyten drangen in den Intercellularraum ein, der nicht ausgedehnt wurde. Die benachbarten Tonofilamente der Keratinocyten blieben normal.
    Notes: Summary Early epidermal lesions of allergic contact dermatitis were examined by electron microscopy. Normal human volunteers were sensitized to DNCB, and contact reactions were elicited sequentially. Epidermal cell changes at 3 h included: the occurrence of small vacuoles with or without membrane, focal dilatation of intercellular spaces, and the alteration of tonofilaments into short, aggregated bundles. Non-sensitized skin to which DNCB was applied also showed small vacuoles with or without membrane. Monocytes infiltrated into the intercellular spaces which were not dilated, and the neighboring tonofilaments of keratinocytes remained normal.
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  • 48
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    Archives of dermatological research 267 (1980), S. 283-290 
    ISSN: 1432-069X
    Keywords: Allergic contact dermatitis ; Infiltrating cells ; Monocytes ; Lymphocytes ; Ultrastructure ; Allergische Kontaktdermatitis ; Infiltratzellen ; Monocyten ; Lymphocyten ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Art und Feinstruktur mononuklearer Zellen, die bei allergischer Kontaktdermatitis nach ungefähr 6 h in der Epidermis auftreten, wurden im Elektronenmikroskop untersucht. Es handelte sich um Monocyten und Lymphocyten, die in ungefähr gleicher Zahl auftraten. Die Ultrastruktur der Monocyten war die gleiche wie die normaler Monocyten im Blut. Offenbar in aktiver Bewegung, erweitern sie die intercellulären Verbindungen der Keratinocyten. Die Lymphocyten zeigten einen runden oder ovalen Kern mit einigem elektronendichten Cytoplasma, das Ribosomen und Polysomen enthielt, aber nur fallweise Mitochondrien und Golgi-Komplexe.
    Notes: Summary The kind and fine structure of mononuclear cells appearing in the epidermis at about 6 h of allergic contact dermatitis were examined by electron microscopy. They were monocytes and lymphocytes, the number being about equal. The ultrastructure of monocytes was that described for normal ones in blood, and apparently actively moving, streching the intercellular connections of the keratinocytes. Lymphocytes displayed a round or oval nucleus with some electron-dense cytoplasm which contained ribosomes and polysomes but only occasional mitochondria and Golgi complexes.
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  • 49
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    Anatomy and embryology 159 (1980), S. 59-69 
    ISSN: 1432-0568
    Keywords: Infrahyoid muscles ; Motoneurons ; Spinal ganglion cells ; Axons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Perikarya of motoneurons and spinal ganglion cells attributed to infrahyoid muscle nerves of the rat were labelled by retrogradely transported horseradish peroxidase (HRP). For the differentiation of motor and sensory axons cross sections of the nerves were stained for acetylcholinesterase. Numbers and diameter distributions of perikarya and myelinated axons were determined. Motoneuronal perikarya innervating the infrahyoid muscles are located from the transition zone brain stem/spinal cord to the segment C 3. They are found mostly in the medial part of the Rexed laminae VII and VIII at the level of C 1 and C 2 and more ventrolaterally in C 3 and are therefore located to a large extent in areas until now not recognized to contain motoneurons. Our results provide evidence for a somatotopic organization of the motoneurons in the upper cervical spinal cord. The diameter distributions of motoneuronal perikarya and axons are in most cases bimodal, the two modes corresponding to α-and γ-motoneurons. In relation to the diameters of their perikarya α-axons are significantly thicker than γ-axons. In contrast to the motoneurons no clear correlation could be established between the sizes of perikarya of spinal ganglion cells and their peripheral processes.
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  • 50
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    Anatomy and embryology 160 (1980), S. 11-27 
    ISSN: 1432-0568
    Keywords: Sertoli cells ; Rat ; Fetal and postnatal life ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sertoli cells have various functions: mechanical (creation of two compartments in the seminiferous tubules, migration of germinal cells), secretory (secretion of anti-Müllerian hormone, inhibin, androgen-binding-protein and estrogen) and phagocytic. We report an ultrastructural study of the rat Sertoli cell during maturation and consider possible correlations between the acquisition of certain morphological characteristics and certain functions. During fetal life, the Sertoli cell possesses differentiated zones of junction with the gonocytes and seems to have a role in the migration of the gonocytes towards the periphery of the seminiferous tubule. The Sertoli cell performs the phagocytosis of the gonocytes which degenerate during their migration, and seems to be the site of production of protein granules, whose presence can be related to the synthesis of anti-Müllerian hormone. After birth and before puberty, when the inclusions resembling secretory granules disappear, the Sertoli cell membranes in contact with spermatocytes II and spermatids differentiate, forming, through the differentiated junctional complexes, two compartments (adluminal and luminal) in the seminiferous tubules. Finally, they acquire the characteristics of active secretory cells, capable, in particular, of steroid synthesis.
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  • 51
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    Anatomy and embryology 158 (1980), S. 167-178 
    ISSN: 1432-0568
    Keywords: Placenta (human) ; Villous stroma ; Intercellular junctions ; Endothelium ; Ultrastructure ; Freeze-fracturing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intercellular junctions within the villous stroma and the cytotrophoblastic layer of the human full term placenta were investigated using thin sectioning and freeze-fracturing. Numerous maculae adherentes (desmosomes) were found between the cytotrophoblast cells and the syncytiotrophoblast. This junction type was also seen connecting adjacent cytotrophoblast cells. Large gap junctions were frequently observed in contact areas of perikarya or at processes of adjacent fibroblasts. They often exhibited a peculiar pattern of their particles on the P-face of the membrane. Small rows of junctional particles were found on the P-faces of interconnected smooth muscle cells and gap junctions frequently bridged myoendothelial and interendothelial contact zones. The significance of the junctional complexes is discussed in relation to functional systems within the villous stroma of the human full term placenta.
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  • 52
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    Anatomy and embryology 158 (1980), S. 349-360 
    ISSN: 1432-0568
    Keywords: Afferent neurons ; Hypoglossal nerve ; Rat ; HRP-tracing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cell bodies of sensory neurons of the rat's hypoglossal nerve were demonstrated by the somatopetal horseradish peroxidase (HRP) transport technique. Labelled perikarya were found within the second and third cervical spinal ganglia and in the vagal sensory ganglia. After application of HRP to the cut peripheral trunk of the hypoglossal nerve about 200 labelled cell bodies were counted in each animal. The vast majority of the axons from cervical spinal ganglion cells reach the hypoglossal nerve via the descending ramus (N. descendens hypoglossi). However, there may exist an additional pathway, probably via the cervical sympathetic trunk. Application of HRP to the medial and lateral end branches led to a labelling of much fewer spinal ganglion cells while the number of labelled vagal sensory neurons remained unchanged. Thus, it is suggested that the majority of the cervical afferents of the hypoglossal nerve originates within the extrinsic tongue musculature and the geniohyoid muscle, whereas the vagal afferents may perhaps derive exclusively from the intrinsic muscles. Histograms of the mean diameters of labelled cell bodies show a predominance of very small perikarya. This contrasts with the diameter distribution of sensory perikarya labelled after HRP application to nerves supplying other skeletal muscles. It is therefore assumed that the afferent component of the hypoglossal nerve is composed mainly of small-calibre axons.
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  • 53
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    Anatomy and embryology 159 (1980), S. 277-288 
    ISSN: 1432-0568
    Keywords: Megakaryocyte ; Bone marrow ; Steel mice ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The megakaryocytes in the bone marrow of steel mutant mice (Sl/Sld) and their normal littermates (+/+) were studied by light and electron microscopy with special emphasis on their maturity and distribution in the hematopoietic cords. A higher percentage of megakaryocytes lying against the sinus wall, a higher percentage of the sinus perimeter covered by megakaryocytes and a higher percentage of large megakaryocytes were found in Sl/Sld mice than in +/+ mice. In addition, more large megakaryocytes as well as senile megakaryocytes were observed in the spleen of Sl/Sld mice than in that of +/+ mice. These observations suggest that more platelets are produced in Sl/Sld mice than in +/+ mice on the basis of per unit area of the marrow tissue. Heretofore, the fate of the senile megakaryocytes in the marrow was not known. However, in Sl/Sld mice senile megakaryocytes were often found entering the marrow sinuses from the hematopoietic cords. They were also seen in the lung and the spleen where degradation of senile megakaryocytes was observed. These observations suggest that senile megakaryocytes in Sl/Sld mice leave the marrow and are removed by the reticuloendothelial system outside the marrow.
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  • 54
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    Anatomy and embryology 159 (1980), S. 289-305 
    ISSN: 1432-0568
    Keywords: Placenta (rat) ; Development ; Intercellular junctions ; Ultrastructure ; Freeze-fracturing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The differentiation of chorionic layers II and III and alterations of intercellular junctions within the developing placental labyrinth were investigated in rats. Between the 14th and 16th day of gestation, the trabecular structures of the labyrinth alter and increasing numbers of primary, secondary, and tertiary lamellae develop. Trophoblastic layer I remains multicellular. Layer III rearranges and cytoplasmic fusions result in a continuous cytoplasmic barrier intervening between the already syncytial trophoblastic layer II and fetal capillaries. Simultaneously, most of the “undifferentiated” cells within the labyrinth disappear. Thin sectioning anf freeze-fracturing reveal multiple images of intercellular junctions, particularly gap and tight junctions in the cellular and syncytial parts of layers II and III. Continuous and regularly arranged tight junctions occur as well as fragmented structures which are spaced irregularly. Gap junctions are occasionally found between the juxtasinusoidal regions of layers II and III on the 14th day. More often they occur within restricted areas near the center of the trabeculae, integrated within extensive tight junctional strands. Gap junctions increase in later stages of pregnancy and eventually become distributed between the interfaces of layers II and III in the primary lamellae.
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  • 55
    ISSN: 1432-0428
    Keywords: Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1–50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p〈0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 μg/ml, elimination was monoexponential with a half-life of 32±11 min (mean±SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
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  • 56
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    Development genes and evolution 188 (1980), S. 65-73 
    ISSN: 1432-041X
    Keywords: Nuclear migration ; Cleavage ; Microtubules ; Ultrastructure ; Gall midge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In the eggs ofWachtliella persicariae the cleavage nuclei move relative to the surrounding ooplasm. This ‘active’ migration is caused by an organelle whose ultrastructure was studied throughout the mitotic cycle. It consists of a greatly enlarged polar cytaster derived from the mitotic apparatus, linked to the nucleus by 100 Å filaments. The microtubules of the cytaster were found only during periods of active nuclear migration, i.e., from the onset of anaphase to the early prophase of the next mitotic cycle. They are always solitary and follow the course of the astral rays, which are known to temporarily adhere to peripheral structures of the egg cell and to exert tractive forces. In contrast to the cytaster microtubules, the microtubules in the spindle are bundled and persist from early metaphase through late telophase. During ontogenesis the first migration cytaster is built up between 3 and 12 min after oviposition near the anterior egg pole, in the vicinity of the sperm nucleus. In non-inseminated eggs time lapse films show a migration cytaster to develop autonomously in a region free from nuclei, but it does not follow the normal path of the male pronucleus. In several cases the female pronucleus, which remains without a cytaster of its own, was observed to move to the cytaster generated in the absence of the male pronucleus. Whether or not it is adhering to a nucleus, the cytaster divides into two at the correct time, i.e, corresponding to the first cleavage division in fertilized eggs. In some non-inseminated eggs this type of ‘pseudocleavage’ has been observed to occur repeatedly, giving rise to an increasing number of anucleate cytasters.
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  • 57
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    Acta neuropathologica 49 (1980), S. 43-49 
    ISSN: 1432-0533
    Keywords: Rat ; Peripheral nerve ; Macrophage ; Ultrastructure ; Histochemistry ; Acid phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cellular content of the endoneurium in peripheral nerves of normal adult rats was studied. Endoneurial cells with high light-microscopical activity of acid phosphatase were usually located close to blood vessels or near the perineurium. Cells with the ultrastructural appearance of macrophages showed the same distribution and accounted for 2–4% of the endoneurial cell nuclei profiles. These cells rapidly endocytosed carbon particles after endoneurial administration of colloidal carbon in vitro.
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  • 58
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    Acta neuropathologica 49 (1980), S. 225-230 
    ISSN: 1432-0533
    Keywords: Human pituitary adenomas ; Tissue culture ; Cell culture ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pituitary adenomas of 120 patients were investigated in tissue and in cell cultures. Under different conditions of culture, the biopsies revealed different rates of growth. In tissue cultures 66% of the samples could be propagated while tumour specimens explanted in cell suspensions proliferated in 80% of the cases. Attempts to establish subcultures were also more successful when specimens were put into cell cultures primarily. Further differences of growth characteristics were observed in connection with the histological types of the parent tissues. According to the old terminology cells of mixed type adenomas had the longest life-span both in tissue and in cell cultures. Considering the proliferative activity, this type of tumour could be most frequently subcultured. Concerning the relationship of different cell components of the biopsies it was proven that survival and proliferation of adenoma cells may occur without fibroblasts. The appearance of fibroblast-like cells in older cultures is a morphological manifestation of the senescence of the specific cell types. Qualitative features of cultured adenoma cells showed that on the basis of cytomorphological properties “chromophobe” samples could be separated from the other types. Cells of acidophil and mixed type growths had the capacity of developing in vitro various migratory shapes, while “chromophobe” cells did not possess this ability. The histological diagnoses made independently from cultures confirmed the tissue culture findings. Differences of in vitro characteristics correlated also with the ultrastructural features of the cultured adenoma cells.
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  • 59
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    Acta neuropathologica 50 (1980), S. 131-138 
    ISSN: 1432-0533
    Keywords: Rat ; Cerebellum ; Vessels ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The adult arrangement and the development of stem vessels and capillaries was studied in the rat cerebellum. In principle, stem vessels branch and terminate at three levels: (1) the molecular layer, (2) the Purkinje cell-granular layer, and (3) the cerebellar white matter. All stem vessels are interconnected by the capillary network which is most dense in the Purkinje cell—granular layer. As in the neocortex, the stem vessels of the cerebellum are formed successively during development, so that the later they are formed the more superficial are their terminations. The formation of multiple stem vessels in the depths of fissures and sulci during both pre- and postnatal development may correlate to regional variations in, e.g., mitotic frequency or thickness of the external granular layer. The earliest “endo-parenchymal” branches are formed before the first neurons are present. Capillary growth by sprouting during the postnatal period parallels known regional differences in the timing of the neuronal maturation, e.g., increased synaptic density and oxidative metabolism. The findings in this investigation confirm and extend the results of an earlier morphometric study on capillary development in the cerebellar cortex. Although the angiogenetic factors remain unknown, the hypothesis of a link between the vascularization and the functional maturation of the brain is corroborated by the results. Knowledge of the normal vascular development seems necessary for an understanding of brain morphogenesis and for interpretation of primary pathogenetic mechanisms in various intoxications etc.
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  • 60
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    Acta neuropathologica 50 (1980), S. 227-232 
    ISSN: 1432-0533
    Keywords: Wallerian degeneration ; Schmidt-Lantermann incisures ; Glycogen clusters ; Peripheral nerves ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phrenic and sciatic nerves of the rat were examined during the initial stages of Wallerian degeneration 4–48 h after axotomy about 5 mm below the level of transection. One of the first changes observed in transected axons was the appearance of glycogen granules and formation of clusters of particulate glycogen at the Schmidt-Lantermann incisures and at the nodes of Ranvier. Four hours after transection, glycogen granules were found at these sites mainly attached to the tubules of axoplasmic reticulum or dispersed in small clusters in the axoplasm. At later stages, glycogen particles increased in number and formed elongated clusters arrayed mostly longitudinally among axonal organelles filling stretches of axons about 2 μm long adjacent to the incisures and in nodal regions. The buld-up of glycogen clusters reached a peak at 22 h after axotomy, when longitudinal arrays of glycogen particles were found at about 70% of the incisures and nodes examined. The percentage of these sites containing glycogen clusters had already decreased 26 h after axotomy. When axonal degeneration advanced and axons contained only floculated material and swollen mitochondria, glycogen granules also disintegrated. It is of interest that glycogen particles accumulate in those regions of the internode where the axon will soon become disrupted during ovoid formation. The possible mechanisms leading to glycogen accumulation at these sites are discussed in relation to the active role of Schwann cells in Wallerian degeneration.
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  • 61
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    Acta neuropathologica 51 (1980), S. 65-70 
    ISSN: 1432-0533
    Keywords: Morphometry ; Glial cells ; Portocaval anastomosis ; Ultrastructure ; Corpus striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure of astrocytes and oligodendrocytes was investigated in rats 10 days, 30 days, and 10 weeks after portocaval anastomosis (PCA). Cell and nuclear sizes were measured by planimetry on randomly sampled cells magnified×24,000. The volume fractions of mitochondria, glia fibrils, and lipofuscin granules were measured in astrocytes by electronic image analysis. The mitochondrial profile area distribution and oligodendrocyte mitochondrial content were likewise estimated. All PCA animals had an increased astrocyte cell and cytoplasmic area, and after correction for cytoplasmic edema all groups had an enhanced mitochondrial fraction and mitochondrial number. The mitochondrial sizes were increased in all PCA groups. The mitochondrial profile area distribution curves did not suggest more than one group of mitochondria. All PCA groups had increased fractions of lipofuscin granules and glia fibrils. The oligodendrocytes had a slight fall in cell, nuclear, and cytoplasmic area after 30 days of shunting, and the mitochondrial fraction was diminished. After 10 weeks of PCA, all changes were reversed to normal values. It is concluded that the astrocytes are the active cells in the brain metabolism of ammonium. The oligodendrocytes seem to be dependent on neuronal integrity and do not contribute to the brain ammonium metabolism. The increase in astrocyte lipofuscin granules content may be explained by a beginning neuronal loss.
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  • 62
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    Acta neuropathologica 51 (1980), S. 113-117 
    ISSN: 1432-0533
    Keywords: Peroxisomes ; Catalase ; d-amino-acid oxidase ; Glial tumors ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphologically and cytochemically defined peroxisomes (microbodies) were demonstrated in a series of 11 human glial tumors. The cytochemical methods used were the diaminobenzidine method for catalase and a tetrazolium salt-phenozine methosulfate method ford-amino-acid oxidase. Ultrastructurally, the peroxisomes were found as single membrane limited organelles with a granular matrix. Marginal plates as well as continuities with the smooth endoplasmic reticulum could be demonstrated. Peroxisomes were found most abundantly in subependymal giant cell astrocytomas, to a lesser number in astrocytomas and least abundantly in glioblastomas.
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  • 63
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    Acta neuropathologica 51 (1980), S. 249-250 
    ISSN: 1432-0533
    Keywords: Neurons ; Mitochondria ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural study of the cerebral cortex and spinal anterior horns disclosed periodically repeating processes located in the envelope space or in the intracristal space of neuronal mitochondria. The alteration was observed in postmortem cases in which fixation was delayed either voluntarity or involuntarily, but was not present in postmortem or surgical specimens in which fixation was prompt. The change is interpreted as an artifact due to delayed fixation.
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  • 64
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    Acta neuropathologica 52 (1980), S. 157-159 
    ISSN: 1432-0533
    Keywords: Neurons ; Thalamus ; Inclusions ; Ultrastructure ; Myotonic dystrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracytoplasmic cosinophilic inclusions were found by light microscopy in the thalamic neurons of 35 consecutive normal adult brains and in a case of myotonic dystrophy, but not in six newborn children, including one with myotonic dystrophy. Histochemical tests suggested a protein composition. Ultrastructurally, the inclusions were composed of stacks of parallel alternating dark and light rectilinear profiles not surrounded by a limiting membrane. Such inclusions are a virtually constant finding in the adult human thalamus and probably represent sites of neuronal protein storage.
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  • 65
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    Acta neuropathologica 50 (1980), S. 221-226 
    ISSN: 1432-0533
    Keywords: Rat ; Brain ; Vessels ; Prenatal ; Development ; Protein deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The internal vascularization of the brain was studied in foetuses of normal and protein-deprived rats from embryonic day (E) 12 to 15. The position of vascular branches showed distinct relations to the various zones of the neuroepithelium. The possibility that various parts of the vascular system may differ in function, maturation, and morphogenetic relations to the neuroepithelium must be considered. The distinct vascular layers were therefore given names relating them to the respective wall zone. The ingrowth of straight stem vessels from the epiparenchymal vascular plexus into the neuroepithelium and the formation of vascular branches close to the ventricular system were referred to as stage I of the internal vascularization. The resulting plexus was called the deep vascular plexus of the ventricular zone. Its formation followed the same temporospatial gradients as the formation of the marginal zone. Following the formation of the intermediate zone, more stem vessels entered the neuroepithelium and a superficial vascular plexus of the ventricular zone was formed (stage II). This plexus was positioned close to the border between the ventricular zone and the intermediate zone. Subsequently, vascular branches also formed plexuses of the intermediate and subventricular zones (stage III). No “intraepithelial” vessels were seen on E 12. The temporospatial gradients in the telencephalic vesicles were caudal to rostral and lateral to medial, starting in the parts corresponding to the ganglionic eminence in the floor of the lateral ventricle on E 13. Only the dorsomedial angles of the hemispheres showed no vessels on E 15. No obvious differences were seen between the normal and the protein-deprived foetuses regarding the timing and extent of vascularization or the size and appearance of wall zones in the immature central nervous (I-CNS).
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  • 66
    ISSN: 1432-0827
    Keywords: Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
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  • 67
    ISSN: 1432-072X
    Keywords: Mating tube ; Microtubule ; Tremella ; Ultrastructure ; Yeast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Ultrastructure of the mating tube formed in yeast haplont of the heterobasidiomycete Tremella mesenterica was studied by electron microscopy. Cell wall of the mating tube emerged as evagination of the inner layers, rupturing outer layers of the mother cell wall. Comparison with budding cells suggested that the tube emergence place at bud scar and the process of tube emergence was the same as that of bud emergence. Electron transparent vesicles of 0.1 μm diameter were scattered in the cytoplasm of the mating tube. Nucleus-associated organelle was located at one side of the nuclear envelope which extended towards the mating tube. A few microtubules were detected in the mating tube, but their association with a nucleus was not clear. The cytoplasmic structure of the mating tube was discussed in comparison with that of hyphae of the filamentous fungi.
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  • 68
    ISSN: 1432-072X
    Keywords: Claviceps purpurea ; Ultrastructure ; Development ; Sclerotium ; Oleosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The development of sclerotia of Claviceps purpurea was investigated by light and electron microscopy. During the first days after infection sterigma and conidiospores are formed. The spores show a moderately developed vacuolar system, they are thick walled and contain about 20% lipid (related to the cell volume) embedded in glycogen. The sterigma are cylindrical unicellular hyphae with electron dense cytoplasm and isolated strongly contrasted lipid droplets. In maturing sclerotia the hyphae become septated with increasingly thick cell walls and a large lipid content. The lipid forms small droplets in young cells, while in the mature sclerotium it occurs in the form of very large drops, occupying the major part of the cell. Simultaneously the composition of the lipid is changed. The mature cells have several nuclei. They are partially connected by osmiophilic substances, forming a network of intercellular spaces.
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  • 69
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    European journal of clinical pharmacology 17 (1980), S. 45-50 
    ISSN: 1432-1041
    Keywords: ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
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  • 70
    ISSN: 1432-1041
    Keywords: sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
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  • 71
    ISSN: 1432-1041
    Keywords: prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
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  • 72
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    European journal of clinical pharmacology 17 (1980), S. 189-196 
    ISSN: 1432-1041
    Keywords: flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
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  • 73
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    European journal of clinical pharmacology 17 (1980), S. 209-213 
    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
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  • 74
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    European journal of clinical pharmacology 17 (1980), S. 215-221 
    ISSN: 1432-1041
    Keywords: L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
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  • 75
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    European journal of clinical pharmacology 17 (1980), S. 425-428 
    ISSN: 1432-1041
    Keywords: prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
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  • 76
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    European journal of clinical pharmacology 18 (1980), S. 25-30 
    ISSN: 1432-1041
    Keywords: pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
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  • 77
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    European journal of clinical pharmacology 18 (1980), S. 109-116 
    ISSN: 1432-1041
    Keywords: diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
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  • 78
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    European journal of clinical pharmacology 18 (1980), S. 517-520 
    ISSN: 1432-1041
    Keywords: desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
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  • 79
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    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Keywords: sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
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  • 80
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    European journal of clinical pharmacology 17 (1980), S. 449-457 
    ISSN: 1432-1041
    Keywords: alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
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  • 81
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    European journal of clinical pharmacology 18 (1980), S. 69-74 
    ISSN: 1432-1041
    Keywords: digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
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  • 82
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    European journal of clinical pharmacology 17 (1980), S. 37-43 
    ISSN: 1432-1041
    Keywords: caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
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  • 83
    ISSN: 1432-1041
    Keywords: bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
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  • 84
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    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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  • 85
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    European journal of clinical pharmacology 18 (1980), S. 83-88 
    ISSN: 1432-1041
    Keywords: patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
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  • 86
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    European journal of clinical pharmacology 18 (1980), S. 147-150 
    ISSN: 1432-1041
    Keywords: antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
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  • 87
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    European journal of clinical pharmacology 17 (1980), S. 295-299 
    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
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  • 88
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    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 89
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    European journal of clinical pharmacology 18 (1980), S. 279-283 
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
    Type of Medium: Electronic Resource
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  • 90
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    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    ISSN: 1432-1041
    Keywords: dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
    Type of Medium: Electronic Resource
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  • 91
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    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    ISSN: 1432-1041
    Keywords: prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
    Type of Medium: Electronic Resource
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  • 92
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
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  • 93
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
    Type of Medium: Electronic Resource
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  • 94
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    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
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  • 95
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    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    ISSN: 1432-1041
    Keywords: naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
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  • 96
    ISSN: 1432-1041
    Keywords: alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-(p-methylallylaminophenyl) propionic acid, alminoprofene (INN), a new antalgic drug, was administered orally to men as a single (300 mg) and multiple doses (300 mg three times daily). Plasma and urine concentrations of alminoprofene were determined by gas-liquid chromatography. After the single oral dose, the peak plasma level (36.2 to 41.5 mg/l) was reached within 0.5–1.5 h. The biological half-life ranged from 2.5 to 3.2 h. During chronic administration of alminoprofene, steady-state equilibrium quilibrium was etablished within 24 h. The urinary excretion of alminoprofene as unchanged product and as glucuronide was very important.
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  • 97
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    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Keywords: pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
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  • 98
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    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
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  • 99
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    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    ISSN: 1432-1041
    Keywords: cefadroxil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
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  • 100
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    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    ISSN: 1432-1041
    Keywords: isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 18 subjects were given isosorbide dinitrate (ISDN) 5 mg sublingually and serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) were measured, as well as changes in digital plethysmographic amplitude, heart rate, ECG, blood pressure and Schellong's test. ISDN was rapidly absorbed and metabolized, having an elimination half-life of 29 min. Its metabolites 2-ISMN and 5-ISMN had longer half-lives of 1.75 and 7.6 h respectively. The amplitude of the α-wave of the digital plethysmograph did not change significantly either in the predrug period or after placebo administration. It increased within 4 min of administration of ISDN, and reached a maximum after 14 min; the effect lasted for about 2 h. ISDN lowers blood pressure and increases heart rate in most volunteers, but in 3 of the 18 subjects severe hypotension occurred, accompanied by severe, reversible bradycardia, which was probably due to vagal reflexes initiated by the markedly diminished ventricular enddiastolic volume (LVEDV) and pressure (LVEDP). No correlation could be demonstrated between the serum concentration of ISDN and/or its vasoactive metabolites and changes in plethysmographic amplitude.
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