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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 565-571 
    ISSN: 1432-1440
    Keywords: Blood-brain barrier ; Drug transfer ; Alkylglycerols
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The penetration of 12 commonly used anticancer agents through the blood-brain barrier (BBB) was measured in a rat model using a single-injection tissue-sampling technique. Two of the tested drugs penetrated the barrier, but only to a limited extent. Entry of the drugs into the brain tissue critically depends on molecular weight and lipophilia of the respective test compound. For drugs with a molecular weight of less than 500, BBB simply behaves like an oil/water interphase, whereas drugs with a molecular weight greater than 500 are practically excluded from transport through the BBB even if they show a favourable oil/water partition coefficient. However, permeability of cytostatics was strongly increased if short chain alkylglycerols, up to final concentrations of about 0.3 mol/l were added to the injected solution. Under these conditions the Brain-Uptake-Index (BUI) reached values up to about 50% (cyclophosphamide), depending on lipid solubility and molecular dimension of the respective test compound and the alkyl chain length of the glycerol derivative.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0942-0940
    Keywords: Somatostatin receptor ; 111Indium-labelled somatostatin analogue ; scintigraphy ; meningioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The recent availability of isotope-labelled somatostatin analogues has allowed one to detect somatostatin receptors in normal tissue as well as in endocrine or non-endocrine cranial tumours. The purpose of the present study was to establish the value of somatostatin receptor scintigraphy using an111Indium-labelled somatostatin analogue, octreotide, in the diagnostic work-up of meningioma patients. Twenty-two patients (16 women, 6 men, aged from 19–70 years) with newly diagnosed, residual or recurrent cranial meningiomas were examined.111Indium-labelled DTPA-octreotide was injected i.V., Planar and tomographic images were obtained with a gamma camera 4–6, and 24 hours after injection. In all of the meningiomas studied a high density of somatostatin receptors was detected by scintigraphy. No false negative test result was found. Due to this, a 100% predictive value of a negative test was calculated. However, when the tumours were taken in culture differing staining intensity could be seen in the light- and electron microscopic level even on individual cells of a single culture when silver intensified somatostatin-gold was used as ligand. We conclude, that in vivo somatostatin receptor scintigraphy may aid in the pre-operative differential diagnosis of skull base tumours.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0942-0940
    Keywords: Cerebral glioma ; somatostatin receptor scintigraphy ; 111In (DTPA-octreotide) ; somatostatin-gold conjugate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Somatostatin receptors (SR) have been identified in vitro in normal brain tissue, in neuro-endocrine tumours and in cerebral gliomas WHO grade 1 or 2 by autoradiography or using somatostatin-gold conjugates. In vivo, SR detection has become possible by scintigraphy applying the somatostatin analogue octreotide, radio-labelled with111Indium. It was supposed that expression of SR in cerebral gliomas corresponds to low grade tumour malignancy and that, in vivo, somatostatin receptor scintigraphy (SRS) could refine and improve the WHO grading system for cerebral gliomas. Nineteen patients with cerebral gliomas (grade 2: n=8, grade 3: n=3, grade4: n=8) were examined with111In (DTPA-octreotide) to evaluate, whether SRS could improve the pre-operative estimation of tumour biology and the postoperative management. The results of SRS were related with the histological findings and with the in vitro demonstration of somatostatin-binding sites on cultured tumour cells incubated with a somatostatin-gold conjugate. In vivo, none of the patients with glioma grade 2 showed enhanced tracer uptake in the SRS, whereas in vitro SR were detected in cultured tumour tissue in 5 out of 5 cases. Every patient with glioma grade 3 or 4 demonstrated a high focal uptake of111In (DTPA-octreotide), as shown by SRS. Three patients with glioma grade 4, additionally examined with 99mTc-DTPA, showed an increased tracer uptake within the tumour area when compared with results of SRS. In vitro, SR were detected on tumour cell surface in 5 out of 6 tissue samples from patients with gliomas grade 3 or 4. One patient harbouring a cerebral abscess presented with a high focal tracer uptake in the SRS but with absence of somatostatinbinding sites in vitro. We concluded, that in glioma patients enhanced tracer uptake in receptor scintigraphy with111In (DTPA-octreotide) does not depend on the presence of SR in tumour tissue but on the dysfunction of the blood-brain barrier. Thus, SRS does not improve the preoperative glioma grading or postoperative management in patients with cerebral tumours of glial origin.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    Journal of neuroendocrinology 13 (2001), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Agonist-induced endocytosis of somatostatin receptors determines subsequent cellular responsiveness to peptide agonist and influences somatostatin receptor scintigraphy, a technique to image various tumours. We examined the internalization of sst3HSV, an epitope-tagged type 3 somatostatin receptor, in transfected rat neuroendocrine insulinoma cells. Stimulation of these cells with somatostatin induced trafficking of coexpressed enhanced green fluorescence protein/β-arrestin1 fusion protein and sst3HSV to colocalize in the same endocytic vesicles. Coexpression of a dominant negative mutant of the arrestin fusion protein with the receptor blocked the internalization of sst3HSV. Stimulation with somatostatin also induced the transient translocation of α-adaptin, a component of the adaptor protein complex 2, to the plasma membrane. α-adaptin and clathrin colocalized with the receptor. By electron microscopy, we observed internalized sst3 in clathrin coated pits, endosomes and at the limiting membrane of multivesicular bodies, a location typical for receptors being recycled. Concordantly, we observed sst3HSV colocalized with Rab11 in a perinuclear compartment which is likely to correspond to the pericentriolar recycling endosome. Thus, agonist-induced endocytosis of sst3 depends on its interaction with β-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 24 (1972), S. 146-148 
    ISSN: 0014-5793
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 107 (1994), S. 111-117 
    ISSN: 1437-1596
    Keywords: Postmortem platelet activation status Platelets ; Immunoelectron microscopy Glycoproteins Gp53, GMP140, thrombospondin ; Thrombozyten ; Aktivierungsstatus Postmortem ; Immunelektronenmikroskopie Glykoproteine Gp53, GMP140, Thrombospondin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Thrombozyten werden durch Substanzen der subendothelialen Matrix in Endothelläsionen oder aktivierte Faktoren der Plasmagerinnungskaskade aktiviert. Umgekehrt aktivieren aktivierte Thrombozyten die plasmatische Gerinnung. Nur aktivierte Thrombozyten exprimieren die Adhäsionsmoleküle Gp53, GMP140 und Thrombospondin auf der Plasmamembran, bei ruhenden Thrombozyten liegen sie intragranulär. Nach Markierung der Glykoproteine mit monoklonalen Antikörpern und Immunogoldlabeling waren Gp53, GMP140 und Thrombospondin an Thrombozyten im Leichenblut elektronen-mikroskopisch ganz überwiegend intragranulär darzustellen. Der intragranuläre Nachweis der Glykoproteine zeigt, daß die Thrombozyten im Leichenblut nicht aktiviert waren. Die Thrombozyten im Leichenblut waren nur im frühen postmortalen Intervall aktivierbar, sie exprimierten dann die Markierungen der Adhäsionsmoleküle auf der Plasmamembran. Später waren sie in vitro auch dann nicht mehr aktivierbar, wenn durch Zugabe von Thrombin der Ausfall von Fibrin provoziert wurde und der Aspekt “geronnenen Blutes” entstand. In der forensischen Medizin könnten diese Befunde hilfreich sein zur Differenzierung intravitaler und postmortaler Gerinnungsvorgänge.
    Notes: Abstract Platelets are activated by substances from the subendothelial matrix in endothelial lesions or by factors in the plasma coagulation cascade. Conversely, activated platelets are potent activators of this cascade. Only activated platelets express the adhesion molecules Gp53, GMP140 and thrombospondin on the plasma membrane. The postmortem activation status of platelets, therefore, can be determined immunoelectron microscopically by immunogold labeling of antibodies against these glycoproteins. Our studies revealed that the vast majority of these antigens were located within the granules post-mortem, hence the platelets had not been activated. Thrombin-induced activation of platelets in vitro was only possible in the early postmortem interval, as demonstrated by labeling of the adhesion molecules on the plasma membrane. Later, such activaton was no longer possible even though thrombin-induced fibrin formation gave the appearance of “coagulated blood”. In forensic medicine, these findings can possibly be applied to distinguish intravital clotting from the postmortem coagulation phenomena and intravital hematomas from postmortemhematomas.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 205 (1980), S. 327-331 
    ISSN: 1432-0878
    Keywords: Somatostatin ; Cortical cells and fibers ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using light microscopic immunohistochemistry, somatostatinpositive structures were observed in the cortex of the rat. These structures, including cells and fibers, are widely distributed in all cortical laminae and are also found in the basal ganglia. The positive results were obtained exclusively in two groups of animals sacrificed during two different months of two subsequent years. The reason for this variability in the immunocytochemical stainability of cortical structures remains enigmatic.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 210 (1980), S. 33-45 
    ISSN: 1432-0878
    Keywords: Luliberin (LRF)-terminals ; Somatostatin-terminals ; Subfornical organ ; Neurohemal regions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary With the aid of light- and electron- microscopic immunocytochemistry, somatostatin- and luliberin (LRF)-positive fibers can be demonstrated in the rat subfornical organ (SFO). Each of the neurohormones has a specific location: LRF in the lateral parts of the organ, and somatostatin in the center of the posterior zone. Common to both neurohormone-containing fibers is the pattern in which they reach the organ as well as the fact that their terminals are located in the perivascular spaces of fenestrated vessels, i.e., within the limited neurohemal regions of the organ. Since injection of India ink of different colors demonstrates that the capillary bed of the SFO is connected with the central capillaries of the choroid plexus, the question arises as to whether the neurohormones released in the area of the SFO influence the choroid plexus.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 189 (1978), S. 479-495 
    ISSN: 1432-0878
    Keywords: Rhombencephalic recess (rat) ; Ependyma ; Circumventricular organs ; Light and electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rhombencephalic recess, an ependymal organ, has been studied for the first time by light- and electron microscopy. It is situated mediosagittally on the floor of the rhomboid fossa at the level of the colliculus facialis. The recess and the superimposed tissue are built up by tanycytes, their apices being connected by tight junctions. HRP horseradish-peroxidase , injected into the c.s.f. cerebrospinal fluid , does not penetrate into the intercellular clefts of the recess area. The recess area reveals a certain autonomy regarding its supply with arteries and capillaries. A bloodbrain barrier exists, but shows slight leakage in circumscribed areas as a result of intense transendothelial vesicular transport. The organization of the recess area is compared with that of other ependymal organs, especially circumventricular organs.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0878
    Keywords: Circumventricular organs (rat) ; Tanycytes ; Tight junctions ; CSF ; blood-milieu
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present study continues a previous investigation on the median eminence (EM) (Krisch et al., 1978). In rats with high levels of neurohormones (LHRH, vasopressin) a limited immunohistochemical labeling of perivascular tanycyte processes can be observed surrounding capillaries in the marginal region of the organum vasculosum laminae terminalis (OVLT) and in the inner part of the subfornical organ (SFO). This labeling extends from the perivascular space a short distance along the tanycyte processes. By conventional electron microscopy and by freeze-etching, tight junctions are demonstrated at a distance from the capillary lumen which corresponds to the borderline of the immunohistochemical labeling of perivascular tanycyte processes in light microscopic preparations. The tight junctions are arranged in several parallel and helical rows and correspond to those found in the median eminence. Consequently, the immunohistochemical labeling in the OVLT and in the SFO marks the intercellular cleft. In the circumventricular organs the immunostaining labels the extension of the perivascular space characterized by the hemal milieu. The perivascular space is separated off by tight junctions from the CSF-milieu of the adjacent neuropil. Furthermore, the present study demonstrates tight junctions in the marginal region of the area postrema (AP) between the perivascular processes of the tanycytes.
    Type of Medium: Electronic Resource
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