Einige Anwendungen eines neuen Reizgerätes

Ohne Zusammenfassung     

The effect of pharmacologically increased blood pressure on brain circulation

Summary The cerebral angiograms of patients with cerebrovascular diseases, head injury and intracranial tumours obtained under normal and pharmacologically increased blood pressure were compared. Changes in cerebral blood flow, circulation time and arterial diameter were examined. CBF was measured by a semiquantitative densitometric method, arterial diameter by a split-image focusing technique.The majority of patients with normal angiograms showed a virtually constant CBF and circulation time, while there was a slight constriction of the arteries. The functional tests during cerebral angiography revealed disturbances of autoregulation in patients with acute cerebrovascular diseases or with intracranial tumours.

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Zusammenfassung An Patienten mit normalen und pathologischen angiographischen Befunden wurden Serienangiogramme bei normalem und medikamentös gesteigertem Blutdruck durchgeführt. Die Auswertung der Angiogramme erfolgte hinsichtlich Strömungsgröße, Gefäßdurchmesser und Zirkulationszeit. Die Durchströmung wurde mit Hilfe einer semiquantitativen densitometrischen Methode bestimmt. Die Messung des Gefäßdurchmessers erfolgte mit einem Schnittbilddickenmesser.Die meisten Patienten zeigten bei Blutdrucksteigerung eine Konstanthaltung der Strömung und der Zirkulationszeiten, während sich die Arterien meßbar kontrahierten. Bei Patienten mit frischen cerebrovasculären Insulten und Hirntumoren ließen sich mit den angiographischen Belastungstesten Störungen der Autoregulation nachweisen.

     

The effect of pharmacologically increased blood pressure on the brain circulation. Angiographic investigation of arterial diameter and blood flow in patients with normal and pathologic angiograms. (Preliminary report)

Summary The cerebral angiograms of patients with cerebrovascular diseases and intracranial tumours obtained under normal and pharmacologically increased blood pressure were compared to those from patients without angiographically detectable lesions. Changes in arterial diameter, circulation time and internal carotid blood flow were examined. Arterial diameter was measured by a split-image focusing technique, internal carotid blood flow by a semiquantitative densitometric method. Patients with a normal angiogram and without clinical evidence of a cerebrovascular disease (so called control group) showed a narrowing of the arteries during acute increase of blood pressure, while internal carotid blood flow and circulation time remained virtually constant.The abnormal behaviour of arterial diameter and circulation in patients with recent cerebral lesions, especially cerebrovascular diseases, and in patients with intracranial tumours is discussed.

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Der Einfluß des pharmakologisch gesteigerten Blutdrukkes auf die Hirnzirkulation. Angiographische Untersuchung des Durchmessers der Hirnarterien und der Strömungs-verhältnisse bei Patienten mit normalem und pathologischem Angiogramm (vorläufiger Bericht)

Zusammenfassung Bei Patienten mit cerebrovasculären Erkrankungen oder Hirntumoren werden die Angiogramme, die unter normalem und pharmakologisch gesteigertem Blutdruck angefertigt worden sind, miteinander verglichen. Als Kontrollgruppe dienten Patienten ohne faßbaren pathologischen Befund im Angiogramm. Die Durchmesser der Hirnarterien werden mit einem Schnittbildverfahren, die Strömung in der A. carotis interna mit einer semiquantitativen densitometrischen Methode bestimmt. Die Patienten der Kontrollgruppe zeigten eine deutliche Arterienkontraktion während der akuten Blutdrucksteigerung. Die Strömung in der A. carotis interna und die arteriovenöse Zirkulationszeit blieben dagegen konstant. Die Bedeutung der gestörten Autoregulation für das von der Norm abweichende Verhalten des Arteriendurchmessers und der Zirkulationszeit unter gesteigertem Blutdruck bei Patienten mit frischen cerebralen Insulten und Hirntumoren wird diskutiert.

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L'influence de l'élévation pharmacologique de la tension artérielle sur la circulation cérébrale. Examen angiographique du calibre des artères cérébrales et de la circulation chez des malades présentants des angiographies pathologiques et normales (rapport préliminaire)

Résumé Les angiographies cérébrales de malades atteints de troubles cérébrovasculaires ou de tumeurs cérébrales sont comparées. Ces angiographies ont été pratiquées sous tension artérielle normale et après élévation pharmacologique de cette dernière. Le groupe de contrôle se compose de malades sans lésion pathologique décelable à l'angiographie. Le calibre des artères cérébrales est mesuré au moyen de la méthode de la ligne coupée, le débit sanguin de la carotide interne par une méthode densitométrique semiquantitative. Les malades sans lésion angiographique décelable présentent une contraction vasculaire nette pendant la phase d'élévation de la tension artérielle. Le débit sanguin de l'artère carotide interne par contre et le temps de circulation restent constants. Le comportement divergeant de la norme aussi bien du calibre vasculaire que du temps de circulation sous élévation de la tension artérielle chez des malades présentant des apoplexies fraîches ou des tumeurs cérébrales est discuté. Il semble que la perte de l'autorégulation est un facteur important.

     

Doxorubicin and daunorubicin induce processing and release of interleukin-1β through activation of the NLRP3 inflammasome

Anthracyclines including doxorubicin and daunorubicin are commonly used for the treatment of both hematologic and solid tumors. Dose related adverse effects often limit the effectiveness of anthracyclines in chemotherapy. Drug-related systemic inflammation mediated by interleukin-1beta (IL-1β) has been implicated in contributing to these adverse effects. The molecular mechanisms underlying anthracycline-mediated expression and IL-1β release are not understood. Elucidating the molecular basis by which anthracyclines upregulate IL-1β activity may present opportunities to decrease the inflammatory consequences of these drugs. Here we demonstrate that doxorubicin induces a systemic increase in IL-1β and other inflammatory cytokines, chemokines and growth factors including TNF-α, IL-6, CXCL1/Gro-α, CCL2/MCP-1, granulocyte colony stimulating factor (GCSF), and CXCL10/IP-10. Studies with IL-1R-deficient mice demonstrate that IL-1 signaling plays a role in doxorubicin-induced increases in IL-6 and GCSF. In vitro studies with doxorubicin and daunorubicin failed to induce expression of proIL-1β in unprimed murine bone marrow-derived macrophages (BMDM) but enhanced the expression of proIL-1β in BMDM that had previously been primed with LPS. Furthermore, doxorubicin and daunorubicin induced the processing and release of IL-1β from LPS-primed BMDM by providing danger signals that lead to assembly and activation of the inflammasome. The release of IL-1β required the expression of ASC, caspase-1, and NLRP3, demonstrating that doxorubicin and daunorubicin-induced inflammation is mediated by the NLRP3 inflammasome. As with other agents that induce activation of the NLRP3 inflammasome, the ability of doxorubicin to provide proinflammatory danger signals was inhibited by co-treatment of cells with ROS inhibitors or by incubating cells in high extracellular potassium. These studies suggest that proinflammatory responses to anthracycline chemotherapeutic agents are mediated, at least in part, by promoting the processing and release of IL-1β, and that some of the adverse inflammatory consequences that complicate chemotherapy with anthracyclines may be reduced by suppressing the actions of IL-1β.     

Internalization and processing of epidermal growth factor in aging human fibroblasts in culture

Tissue culture lines established from newborn human skin were used as a model system to study the effects of the mitogenic hormone epidermal growth factor (EGF) on the aging process. These cells demonstrated a finite life span in culture which is presumed to be related to the in vivo aging process. Fibroblasts aged in vitro demonstrated a reduction in their ability to respond to the mitogenic effects of EGF as compared to these cells at an earlier population doubling level (PDL). This decreased responsiveness was not due to a decrease in the number of EGF receptors/cells, as cells at late PDL possessed either the same or more EGF receptors than cells at an earlier PDL. In Rat-1 fibroblasts, 125I-labeled EGF is internalized following binding to the surface receptor, and is transported through intracellular organelles where it undergoes a series of modifications which result in acidification of the EGF (Matrisian et al., 1984, J. Biol. Chem. 259, 3047). It is not known whether this acidic processing of EGF is necessary for mitogenic activity. EGF internalization and processing were therefore examined in aging human fibroblasts to determine if the decrease in EGF responsiveness is due to an alteration in EGF processing. Human fibroblasts internalized and processed pI 4.55 125I-labeled EGF to the more acidic pI 4.2, 4.35, and 4.0 species in a manner similar to Rat-1 fibroblasts. The nature of the processed product and the time course of processing was the same in cells at early and late passages. We therefore conclude that the decreased responsiveness of aged cells to EGF is not due to a defect in the EGF-processing mechanism.     

Phorbol diester and epidermal growth factor receptors in 12-O-tetradecanoylphorbol-13-acetate-resistant and -sensitive mouse epidermal cells

Several cell variants have been isolated from promotable mouse JB6 epidermal cells which are resistant either to mitogenic stimulation at quiescence or to promotion of anchorage independence by 12-O-tetradecanoylphorbol-13-acetate (TPA). Such resistant variants would be expected to lack one or more steps in the TPA response pathway leading to mitogenesis or promotion of tumor cell phenotype. This report is concerned with determining whether resistance is attributable to lack of receptors for phorbol diesters or epidermal growth factor (EGF, a potential mediator) or to absence of receptor down modulation following ligand binding. The results show that neither lack of phorbol diester receptors nor absence of down modulation can be demonstrated in the TPA-resistant variants. The phorbol ester binding affinity is also not altered in the resistant variants. The presence of EGF receptors cannot be an absolute requirement for TPA promotion sensitivity since three of the TPA-promotable cell lines lack available EGF receptors. Lack of EGF receptors may account for TPA mitogen resistance in at least three of four resistant variants. The TPA-induced EGF binding decrease occurs in both sensitive and resistant variants. Thus, phorbol diester binding and receptor down modulation remain as possible required events in mitogenic and promotion responses to TPA. EGF receptors are clearly not necessary for TPA promotion of anchorage independence in JB6 cells but may mediate mitogenic stimulation of these cells by TPA.     

Experimentelle Untersuchungen über die Behandlung des Status epilepticus

Zusammenfassung Nach einer kurzen Darstellung der Möglichkeiten zur experimentellen Prüfung krampfhemmender Substanzen wird eine Methode angegeben, die mit Hilfe des Elektrocorticogramms eine quantitative Bestimmung der Krampfintensität und ihrer pharmakologischen Beeinflußbarkeit erlaubt. Dabei erfolgt die Auslösung der einem Status epilepticus gleichenden Krampftätigkeit durch lokale Strychnineinwirkung auf die Hirnrinde. Mit dieser Methode wurden mehrere Substanzen auf ihre krampfunterbrechende Wirksamkeit untersucht. Während Luminal und Zentropil regelmäßig die Krampfserien unterbrachen, führte Cardiazol zu einer vorübergehenden Steigerung und anschließend zu einem Abfall der Krampfaktivität. Coramin, Hydergin und Megaphen zeigten keine Wirkung. Im künstlichen Winterschlaf kam es zu einer Steigerung der Krampftätigkeit bis zur Entstehung eines pausenlosen Dauerkrampfes. Die Wirksamkeit des Luminals war im künstlichen Winterschlaf potenziert. Abschließend wird versucht, die Wirkungsweise antikonvulsivischer Mittel zu deuten.Mit 4 Textabbildungen.Auszugsweise vorgetragen auf der 4. Tagung der Deutschen EEG-Gesellschaft, Köln, 1954.     

Embolism during cerebral angiography

Summary During angiographic investigations fibrin clots can form in the puncturing needle or in the catheter. Occasionally these pass into the brain arteries during contrast medium injection. The angiographic characteristics of these embolisms, which happened in 7 out of 1000 crebral angiographies, are demonstrated. In our own 4 cases with contral angiogram it is shown that these emboli dissolve in a short time, without any therapeutic measures. Fortunately, neurological complications due to these emboli seem to be rare.

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Zusammenfassung Während angiographischen Untersuchungen können sich in der Punktionsnadel oder im Katheter frische Fibrin-Gerinnsel bilden. Gelegentlich gelangen diese während der Kontrastmittelinjektion in die Hirnarterien. Die angiographischen Charakteristika dieser Embolien werden an Hand von 7 eigenen Beobachtungen bei 1000 cerebralen Arteriographien beschrieben. In 4 eigenen angiographisch kontrollierten Fällen lösten sich diese Emboli innerhalb einer kurzen Zeit ohne jegliche therapeutische Maßnahme auf. Glücklicherweise scheinen neurologische Komplikationen bei dieser Art Emboli selten zu sein.

     

Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody

Hemolytic-uremic syndrome (HUS) results from infection by Shiga toxin (Stx)-producing Escherichia coli and is the most common cause of acute renal failure in children. We have developed a mouse model of HUS by administering endotoxin-free Stx2 in multiple doses over 7 to 8 days. At sacrifice, moribund animals demonstrated signs of HUS: increased blood urea nitrogen and serum creatinine levels, proteinuria, deposition of fibrin(ogen), glomerular endothelial damage, hemolysis, leukocytopenia, and neutrophilia. Increased expression of proinflammatory chemokines and cytokines in the sera of Stx2-treated mice indicated a systemic inflammatory response. Currently, specific therapeutics for HUS are lacking, and therapy for patients is primarily supportive. Mice that received 11E10, a monoclonal anti-Stx2 antibody, 4 days after starting injections of Stx2 recovered fully, displaying normal renal function and normal levels of neutrophils and lymphocytes. In addition, these mice showed decreased fibrin(ogen) deposition and expression of proinflammatory mediators compared to those of Stx2-treated mice in the absence of antibody. These results indicate that, when performed during progression of HUS, passive immunization of mice with anti-Stx2 antibody prevented the lethal effects of Stx2.