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  • Artikel: DFG Deutsche Nationallizenzen  (24)
  • 1990-1994  (3)
  • 1970-1974  (21)
Datenquelle
  • Artikel: DFG Deutsche Nationallizenzen  (24)
Materialart
Erscheinungszeitraum
Jahr
  • 1
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 14 (1974), S. 1-9 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 281 (1974), S. 47-56 
    ISSN: 1432-1912
    Schlagwort(e): Botulinum A ; Tetanus ; Neurotoxin ; Hemagglutinin ; Iodine Labeling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Labeling of crystalline botulinum A toxin has been done with 125I by aid of the chloramine T method. The neurotoxic component is well preserved, whereas the hemagglutinin undergoes physicochemical alterations. Neither with labeled nor with unlabeled toxin, hemagglutinating power parallels the main protein peak. 2. Neurotoxin, homogeneous in gel filtration, is bound to synaptosomes from rat brain. Cold toxin competes with labeled toxin, and antitoxin or neuraminidase partially remove the bound neurotoxin. 3. Upon intramuscular injection, some radioactivity is recovered in the respective parts of the spinal cord. Antitoxin prevents the ascent. The similarities between tetanus and botulinum A neurotoxins are stressed.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 402-416 
    ISSN: 1432-1912
    Schlagwort(e): Snake Venom ; Blood Coagulation ; Prothrombin ; Hemorrhage ; Proteolysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. The procoagulant from Echis carinatus venom, which is known to convert prothrombin into thrombin, has been purified by chromatography on calcium hydroxylapatite and DEAE cellulose. Final purification, when necessary, can be achieved by disc gel electrophoresis. A final concentration of 0.5 μg/ml coagulates human citrate plasma in 70 sec. 2. The bulk of hemorrhagic, caseinolytic and fibrinogenolytic activities present in the starting venom is removed during purification, but the procoagulant causes some fibrinogenolysis, gelatinolysis, caseinolysis and hemorrhage, even when homogenous in disc gel electrophoresis. This argues for a proteolytic nature of the procoagulant activity. It is resistant against diisopropyl fluorophosphate and is not, therefore, an esteroprotease. Other protease inhibitors (from soy bean, lima bean, bovine pancreas and bovine serum) are also without effect. 3. The molecular weight is approximately 86 000, as determined by gel filtration. On isoelectric focusing in solution, its isoelectric point is pH 4.4±0.1. The procoagulant is relatively unstable; for instance, its pH-stability is restricted to values between 6 and 10.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 1-19 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin-Labelled Protein ; Spinal Cord ; Pharmaco-kinetics ; Radioimmunassay ; Tetanustoxin ; Markierte Proteine ; Rückenmark ; Phar-makokinetik ; Radioimmunassay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. The preparation and properties of125I-labelled tetanus toxin are described. 2. After intravenous injection there is a short phase when the labelled toxin is rapidly removed from the blood plasma. This initial period is followed by a slow second phase of decay which has a longer duration. The first phase in very pronounced in rabbits, but not in rats. Unlabelled toxin is removed equally fast from rabbit plasma, as has been revealed by measuring the immunological reactivity (so-called “junction test”) and toxicity. 3. Thirty minutes after i.v. administration torabbits about 2/3 of the radioactive label are found in the liver. The highest concentration is attained in the spleen. 24 hours later, the bulk of the label has been excreted in the urine and faeces, which indicates catabolism of the toxin. In therat, the concentration in the liver is much less prominent, and the excretion of the label is slower. In both species, the central nervous system does not accumulate more than just measurable quantities of the label, even if the animals are given large toxic doses. 4. After injection into the left gastrocnemius muscle of the rat, the labelled tetanus toxin is absorbed very slowly from the site of administration. It is taken up by the corresponding N. ischiadicus and the lumbar region of the spinal cord. The injection of toxin into the anterior leg leads to concentration of radioactivity in the cervical area of the medulla. The arrival of the label in the spinal cord coincides approximately with the appearance of local tetanus. Sectioning of the N. ischiadicus prevents the appearance of the local tetanus of the lower extremity. The enrichment of the toxin in the lumbar cord is prevented in operated, but not in sham-operated rats. 5. When the spinal cord was subdivided into four sectors, the label was found to be greatly concentrated in the ipsilateral ventral sector of the segment corresponding with the injected extremity. This indicates transport into the ventral roots. 6. 131I-labelled tetanus antitoxin also disappears very slowly from the rat gastrocnemius. In contrast to labelled tetanus toxin, however, it is not concentrated in the spinal cord.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 399-420 
    ISSN: 1432-1912
    Schlagwort(e): Vascular Permeability ; Haemorrhage ; Basement Membrane ; 125J-Human Albumin ; 51Cr-Erythrocytes ; GefÄ\permeabilitÄt ; HÄmorrhagie ; Basalmembran ; 125J-Humanalbumin ; 51Cr-Erythrocyten
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Rabbits first received51Cr labelled erythrocytes and then125J-labelled human serum albumin intravenously, followed by the intracutaneous administration of the agents to be tested. The skin areas were excised and evaluated for escape of albumin and red blood cells. Three modes of vascular alteration have been distinguished: a) Increase of permeability for solutes, but not for erythrocytes, as caused by histamine and bradykinin (type I). b) True haemorrhage, as induced by collagenase or the snake venom factor called HR1. No prior increase of albumin permeability has been observed when following the dependence of collagenase action on time or when measuring the ratio between dose and effect, which is linear. Haemorrhage is always accompanied by escape of some additional protein (type II). c) Alterations of a mixed type, as caused by trypsin and chymotrypsin, to a lesser extent by the tenside lysolecithin. Haemorrhage is preceded and accompanied by massive leakage of albumin. For trypsin and chymotrypsin, the dose response ratio is semilogarithmic over a wide range, whereas for lysolecithin it is linear. Hyaluronidase is ineffective in rabbit vessels but enhances the escape of albumin in rats. Histamine release may be relevant as intermediary step since systemic pretreatment with mepyramine is partially preventive. 2. In order to correlate the in vivo findings with biochemical changes, glomerular basement membranes from rats were incubated with the agents mentioned. The release of proteins and peptides was measured by a modification of Folin's method. a) Bradykinin, histamine, and hyaluronidase are ineffective. b) The tenside lysolecithin solubilizes proteins and peptides when applied in high concentrations only. c) Collagenase and HR1 are about equieffective. d) Trypsin and chymotrypsin are about ten times more active than collagenase and HR1. 3. Therefore, haemorrhage and increase of albumin permeability are two clearly distinct phenomena. Our results support the following working hypothesis: Haemorrhage is due to damage of the stabilizing apparatus of the vessel, e.g. basement membranes and surrounding fibrils; the barrier for albumin, however, is to be sought in the endothelial layer of typical capillaries.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 177-182 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Iodine Labeling ; Spinal Cord ; Histoautoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 125I-labeled tetanus toxin was injected intravenously and intramuscularly in rats. Specific localisation within the spinal cord was obtained by histoautoradiography. 1. In generalized tetanus grain density was maximal in the ventral grey matter of spinal cord. The grains were closely correlated to the motoneurons and their neuropil. Other areas showed background activity only. 2. In local tetanus the injected side was labeled selectively. High grain density regularly covered a distinct group of motoneurons and their neuropil. 3. There is some evidence for intracellular accumulation of the toxin since the maximum of grain density was found over the perikarya whilst the nucleus corresponded to a minimum. 4. Cells yielding high grain density were less intensively stained with toluidine blue than neighbouring unlabeled cells. It is concluded from these experiments that tetanus toxin develops its action within or around selected motoneurons and that it induces morphological alterations there.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 327-340 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Pharmacokinetics ; Central Nervous System ; Iodine Labelling ; Receptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In order to understand the symptomatology of generalized tetanus from the pharmacokinetics of the toxin, 125I-labelled toxin was injected i.v. in rats without and with antitoxin. 1. After a few hours latency, brain stem and spinal cord concentrate radioactive material up to the third day. The decline of radioactivity is very slow, semilogarithmic, and can be followed up to the 24th day after injection. In contrast, forebrain and cerebellum do not bind measurable radioactivity. Less than 1% of the radioactivity injected is found in the CNS. 2. The symptoms of tetanus start some time after the bulk of labelled toxin has been taken up by the CNS. They cease before all radioactivity has left it. 3. Antitoxin, given simultaneously, prevents the onset of symptoms and the uptake of radioactivity by the CNS. When given 10 h after labelled toxin, it nearly abolishes the fixation and still prevents the onset of symptoms. When given 48 h after toxin, it is nearly ineffective in both respects. Antitoxin first delays, then enhances the elimination of labelled toxin from the blood. 4. Labelled antitoxin is not enriched in the CNS. 5. The uptake of radioactivity into various parts of spinal cord corresponds well to their relative content in grey matter. 6. The pharmacokinetic behaviour of 125I-toxoid resembles that of toxin. However, in order to get measurable fixation to the CNS at least 50 times higher amounts are to be applied. It is concluded that the barrier between blood and CNS is practically impermeable to tetanus toxin. The results can be harmonized best with the assumption that generalized tetanus is nothing else than a multiple local tetanus.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 341-359 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus Toxin ; Iodine Labelling ; Central Nervous System ; Receptors ; Antitoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Lyophilized homogenate of rat brain binds 125I-labelled tetanus toxin better than does homogenate from spinal cord. This is in contrast to the in vivo behaviour of the toxin where it is bound only to spinal cord. Liver homogenate does not fix the toxin. 2. Autoradiography of preincubated slices from spinal cord shows that the radioactivity is evenly and nearly exclusively bound to gray matter. 3. Maximally 40% of the labelled material interacts with brain homogenate. The toxicity of the remaining supernatant is much more reduced than is its radio-activity. 125I-toxoid, prepared from labelled toxin by treatment with formol, is bound only very weakly. Thus we assume that our toxin preparation is already partially toxoided, and that binding to CNS matter bears some relevance to toxicity. 4. The fixation of the labelled toxin is reversible. The degree of reversibility depends on the conditions used. Binding can be nearly completely reversed or prevented by treatment with antitoxin, but not more than 50% of the binding is reversed by treatment with unlabelled toxin. Repeated washings also remove the bulk of the initially bound toxin. Thus binding sites with different affinities are to be assumed. 5. A complex between ganglioside and cerebroside binds the labelled toxin more firmly than does brain homogenate. No competition between unlabelled and labelled toxin has been observed for this solid phase. Antitoxin nearly completely prevents and largely reverses the fixation of labelled toxin. 6. On the basis of the selective, competitive reactivity of labelled and unlabelled tetanus toxin with brain matter, a radio receptor assay has been developed. It can be used for the measurement of tetanus toxin down to 5 ng. 7. Gradient centrifugation of sucrose homogenates preincubated with labelled toxin reveals one peak of radioactivity in the fractions where the synaptosomes are to be expected; the larger part of the toxin remains, however, unevenly distributed near the starting volume. 8. Desoxycholate solubilizes the complex between labelled toxin and brain matter with parallel dissolution of brain proteins. 9. Neither brain nor spinal cord homogenates degrade labelled toxin into TCA-soluble fragments at pH 7.5. Partial degradation occurs, however, at pH 3.5.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 321-326 
    ISSN: 1432-1912
    Schlagwort(e): Tetanus ; Antibodies ; Radioimmunological Measurement
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A radioimmunological assay procedure allows the measurement of small amounts of tetanus antibodies; it should also be applicable to antibodies against other soluble antigens. It is based on the competition between dissolved and solid phase antibodies for labelled antigen. In the range of experimental error, the same antibody titers are found with the radioimmunological and with the mouse protection test. The detection limit is in the range of 0.001 IU/ml. The reaction conditions allow the determination of antibodies in multiple samples.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 270 (1971), S. 1-9 
    ISSN: 1432-1912
    Schlagwort(e): Melittin ; Peptides ; Venoms ; Hemolysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The hexacosapeptide melittin I, which is the main toxin of bee venom, has been synthesized by Lübke and Schröder. In addition, the following derivatives have been prepared which are probably also present in bee venom: melittin II (which differs by one serine), and N1-formylated melittin I and II. In pharmacological tests, the four synthetic peptides were qualitatively indistinguishable from natural melittin as prepared from bee venom. Theyhemolyzed rabbit erythrocytes with a flat dose-response curve. Melittin I exerted 92% of the activity of the natural substance, the three other peptides 90, 61 and 52% respectively.-Theirsurface activity was between 86 and 96% of that of the natural material.-In contrast to our previous reports, no differences were found in onset, degree and duration of the shortlastinghypotensive action in rabbits.-Toxicity (LD 50, mice) was about 4 mg/kg for natural melittin and for the synthetic melittins I and II. The toxicity of formylated melittins was not very different.-The five compounds caused a slow and prolongedcontraction of the guinea-pig ileum which led to tachyphylaxis. Peptide mapping confirmed the identity between the main compound of natural melittin and synthetic melittin I. The peptide pattern of synthetic melittin II is different and is further modified by the presence of the N-formyl group. Our findings leave no doubt as to the identity between the bulk of natural melittin and melittin I. They corroborate the presence in natural melittin of small amounts of N1-formylated melittin I. The pharmacological similarities to synthetic melittin II and N1-formylated melittin II (which have not yet been identified in the venom) argue for a broader structural basis of the melittins as a group.
    Materialart: Digitale Medien
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