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  • 1
    ISSN: 1432-1238
    Keywords: Septic shock ; Cyclic GMP ; Guanylyl cyclase ; Human ; Atrial natriuretic peptide ; Vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). Design Prospective clinical investigation. Setting Medical intensive care unit of a university hospital. Patients 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and —in some cases — hemodialysis. Measurements and results Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84±1.52 pmol·ml−1) than in healthy controls (1.77±0.18 pmol·ml−1,p〈0.0001), in septicemia patients without circulatory failure (3.28±0.36 pmol·ml−1,p〈0.005) or in patients with hyperkinetic non-septic shock (3.6±0.7 pmol·ml−1,p〈0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. Conclusion These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 113 (1987), S. 298-300 
    ISSN: 1432-1335
    Keywords: Ehrlich ascites tumor cells ; DNA over-replication ; Anaerobiosis ; G2M phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary G2-enriched fractions of Ehrlich ascites tumor cells (up to 80%–85% G2 cells) separated from anaerobically and aerobically cultured asynchronous populations by centrifugal elutriation revealed the same growth characteristics after recultivation under standard conditions: a significant proportion of cells with increased DNA (DNA content〉4C) emerged. Interruption of DNA synthesis by deprivation of oxygen may account for polyploidisation (over-replication) of DNA but other mechanisms must be taken into consideration.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 18 (1992), S. 309-311 
    ISSN: 1432-1238
    Keywords: Methylene blue ; Septic shock ; Human ; Multiorgan failure ; Nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation an hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg·kg−1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 115-122 
    ISSN: 1432-1335
    Keywords: Acetat ; Anaerobiose ; Lipogenese ; Oktanoat ; Pyruvate ; Tritiiertes Wasser ; Tumor ; Acetate ; Anaerobiosis ; Lipogenesis ; Octanoate ; Pyruvate ; Tritiated water ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.
    Notes: Zusammenfassung Unter anaeroben Kulturbedingungen, (95% Argon 5% CO2) stieg der Gesamtlipidgehalt in Ehrlich Ascites Tumorzellen etwas stärker an als unter aeroben Bedingungen (20% O2, 75% N2, 5% CO2). In Abwesenheit von Sauerstoff war der Einbau von [U-14C]Acetat in die Gesamtlipidfraktion als auch in einzelne Lipidklassen, deutlich erhöht, wohingegen ein drastischer Abfall der Einbauraten aus [U-14C]Pyruvat und [1-14C]Oktanoat sowie eine signifikante Verminderung des Einbaus von 3H-Wasser unter diesen Kulturbedingungen beobachtet wurde. Da die spezifische Aktivität von intrazellulärem Wasser auch unter tiefgreifenden Änderungen des metabolischen Zustandes der Zellen praktisch konstant bleibt, wird 3H-Wasser als die zuverlässigste Vorstufe zur Messung der Lipidbiosynthese unter aeroben und anaeroben Kulturbedingungen angesehen. Aus den Ergebnissen wird geschlossen, daß Ehrlich Ascites Tumorzellen nicht, wie es für Normalgewebe angenommen wird, in der Lage sind, NADH/NADPH bei Ausschluß von Sauerstoff durch erhöhte Fettsäuresynthese zu, reoxidieren. Der beobachtete Anstieg im Gesamtlipidgehalt von anaerob kultivierten Zellen erklärt sich wahrscheinlich durch ein Ungleichgewicht zwischen normaler Aufnahme und gehemmtem Abbau von exogenen Lipiden.
    Type of Medium: Electronic Resource
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