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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; diabetic nephropathy ; G protein activation ; cellular signalling ; lymphoblasts ; platelet-activating factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic susceptibility contributes significantly to the risk of developing nephropathy in insulin-dependent diabetes mellitus (IDDM). The cellular substrate for this has remained enigmatic. We investigated whether afflicted IDDM patients display an enhanced activation of pertussis toxin (PTX)-sensitive G proteins, a phenomenon which has been demonstrated in patients with essential hypertension. We established immortalised B lymphoblast cell lines from 10 IDDM patients without nephropathy (DC) and 15 IDDM patients with nephropathy (DN). Nephropathy was defined as a persistent albumin excretion rate of more than 20 μg/min (DC 3.9 ± 5.8, DN 562.3 ± 539.0 μg/min, respectively). Subjects were matched with regard to age (DC 28.9 ± 6.5, DN 35.9 ± 9.9 years), diabetes duration (DC 19.3 ± 6.9, DN 22.7 ± 5.8 years) and HbA1 c values (DC 8.5 ± 1.4, DN 8.8 ± 1.6 %). Reactivity of PTX-sensitive G proteins was quantified by measuring platelet-activating factor (PAF)-induced Ca2 + mobilisation (fura 2 method) and by mastoparan-stimulated [35S]GTPγS binding. Expression of Gαi proteins was quantified by Western blot analysis. PAF-evoked Ca2 + increases above baseline averaged 77.0 ± 52.5 nmol/l in DC and 150.7 ± 61.5 nmol/l in DN (p = 0.005). PAF-evoked Ca2 + increases correlated with stimulated [35S]GTPγS binding (r 2 = 0.42, p = 0.012). From Western blot analysis an overexpression of Gαi proteins could be excluded in DN. A consequence of the altered metabolic milieu in diabetes is the increased release of vasoactive and proliferative agonists which promote glomerular hyperfiltration, hypertrophy, enhanced matrix deposition, and, finally, glomerulosclerosis. Many of these auto- and paracrine agonists bind to G protein-coupled receptors. Therefore, their cellular effects are reinforced by the enhanced G protein reactivity and increase the propensity to nephropathy in IDDM. [Diabetologia (1998) 41: 94–100]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1238
    Keywords: Key words Hemofiltration ; Systemic inflammatory response syndrome ; Tumor necrosis factor α ; Interleukin-6 ; Clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To test the hypothesis that continuous hemofiltration increases interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) clearances and results in decreased cytokine plasma concentrations independent of renal function in patients with early SIRS. Design: Prospective, controlled, randomized study. Setting: Intensive care units at a university hospital. Patients: 28 consecutive patients who fulfilled the criteria of the systemic inflammatory response syndrome (SIRS). Interventions: Patients with SIRS were randomly assigned to either a hemofiltration or a control group irrespective of renal function. In patients of the hemofiltration group an isovolemic hemofiltration was initiated directly after the diagnosis of SIRS and maintained for at least 48 h. Measurements and results: A significant (p 〈 0.001) increase in total IL-6 clearance (hemofiltrate + urine), but not in TNFα clearance, was observed with hemofiltration. However, the plasma concentrations of both cytokines remained unchanged. Hemodynamic variables did not change significantly. Conclusions: Continuous hemofiltration increases IL-6 plasma clearance but not TNFα clearance. However, hemofiltration failed to decrease plasma concentrations of TNFα and IL-6 and, therefore, cannot be used effectively for cytokine elimination in SIRS. Accordingly, beneficial effects occasionally reported with hemofiltration are unlikely to be expected due to elimination of IL-6 or TNFα.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Epinine (N-methyl-dopamine) ; Dopamine ; Prolactin ; Dopaminergic receptors ; Adrenergic receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and α- and \-adrenoceptors. To study whether in vivo DA-receptor mediated effects can be separated from α- and \-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 μg/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and α- and \-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h preinfusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 μg doses dopamine and epinine did not affect Psyst Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine, dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure-and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst-and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by bisoprolol and was converted into a heart rate-decrease by propranolol. We conclude that in 0.5 and 1 μg doses (plasma levels of 20–80 nmol/1) epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3 × 100 mg/day with peak plasma epinine-levels of 50–80 nmol/1) very likely activates only DA-receptors. In higher doses, however, epinine -like dopamine - activates α- and \-adrenoceptors whereby epinine has a stronger α-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Key words Epinine (N-methyl-dopamine) ; Dopamine ; Prolactin ; Dopaminergic receptors ; Adrenergic receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and α- and β-adrenoceptors. To study whether in vivo DA-receptor mediated effects can be separated from α- and β-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 μg/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and α- and β-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 μg doses dopamine and epinine did not affect Psyst, Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition, both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine, dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure- and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by biso-prolol and was converted into a heart rate-decrease by propranolol. We conclude that in 0.5 and 1 μg doses (plasma levels of 20–80 nmol/l) epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3×100 mg/day with peak plasma epinine-levels of 50–80 nmol/l) very likely activates only DA-receptors. In higher doses, however, epinine - like dopamine - activates α- and β-adrenoceptors whereby epinine has a stronger α-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Rapid progressive (crescentic) glomerulonephritis ; Postinfectious glomerulonephritis ; Membrane plasma separation ; Immunosuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since 1971 we observed 31 patients with histologically proven rapidly progressive (crescentic) glomerulonephritis. At the onset of therapy 16 patients presented with end stage renal failure, the others with impaired renal function. 21 patients received combined immunosuppressive therapy, consisting of prednisone, cyclophosphamide and azathioprine. 8 patients were treated with membrane plasmapheresis, additionally. 10 patients received no specific therapy. After 5 years 13 patients were on hemodialysis, 4 had impaired renal function and 10 patients were dead. Two patients died due to the progression of underlying diseases, the others were lost following infectious diseases. There was no additional positive effect in the group treated with membrane plasma separation compared with patients treated only immunosuppressive. Only in 4 patients without specific therapy normalization of renal function occurred. In these patients RPGN appeared after an infectious disease. We conclude that an infectious disease associated RPGN is an own entity of glomerulonephritis that has a very good prognosis and needs only antibiotic therapy.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1912
    Keywords: Key words Noradrenaline (i.v.) ; Tyramine (i.v.) ; Adrenoceptors ; Muscarinic receptors ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed firstly to compare the in vivo cardiovascular effects of exogenously administered and of endogenously released noradrenaline; secondly to characterize the adrenoceptors mediating these responses; thirdly to assess the influence of parasympathetic tone on the cardiovascular effects of noradrenaline. In two randomised placebo-controlled studies, healthy, young, male volunteers received intravenous (i.v.) infusions of noradrenaline at six incremental doses of 10–160 ng/kg/min and – in order to release endogenous noradrenaline – tyramine at four incremental doses of 5–20 μg/kg/min. Noradrenaline and tyramine were administered in the absence and presence of α1-adrenoceptor blockade with doxazosin (2 mg p.o.), α2-adrenoceptor blockade with yohimbine (15 mg p.o.), selective β1-adrenoceptor blockade with bisoprolol (15 mg p.o.) and muscarinic receptor blockade with atropine (15 μg/kg i.v. loading dose followed by 0.15 μg/kg/min by i.v. infusion). Vasoconstrictor effects were assessed by measurement of diastolic blood pressure (Pdiast) and myocardial effects by measurement of systolic time intervals, namely the duration of electromechanical systole corrected for heart rate (QS2c). I.v. noradrenaline increased Pdiast (Δmax 17 mmHg) and this was nearly completely suppressed by doxazosin but only slightly blunted by yohimbine. Noradrenaline also slightly shortened QS2c (Δmax –22 ms), and this was potentiated by both doxazosin and yohimbine and completely blocked by bisoprolol. I.v. tyramine reduced Pdiast (Δmax –7 mmHg), which was not affected by α1-adrenoceptor blockade, and profoundly shortened QS2c (Δmax -104 ms) which was significantly correlated with a marked increase in systolic blood pressure (Psyst) (Δmax 57 mmHg). The shortening of QS2c and the rise in Psyst were not influenced by α-adrenoceptor blockade but were antagonized by bisoprolol. Atropine potentiated the blood pressure rise and the shortening of QS2c induced by i.v. noradrenaline and converted the fall in Pdiast induced by i.v. tyramine into an increase. Thus the cardiovascular effects of exogenous noradrenaline are mainly characterized by α1-adrenoceptor-mediated vasoconstriction and the actions of endogenous noradrenaline (released by i.v. tyramine) by β1-adrenoceptor-mediated positive inotropic effects. The rise in Psyst with i.v. tyramine most likely reflects positive inotropism and not a vascular ‘pressor’ response.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Key words Noradrenaline (i.v.) ; Tyramine (i.v.) ; Adrenoceptors ; Muscarinic receptors ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study, carried out in six elder healthy volunteers (mean age: 61 years), was to determine the influence of muscarinic receptor blockade with atropine (15 µg/kg i.v. loading dose followed by 0.15 µg/kg/min by i.v. infusion) on the effects of i.v. infusions of noradrenaline (5 incremental doses of 10-120 ng/kg/min) or tyramine, that releases endogenous noradrenaline (4 incremental doses of 5-20 µg/kg/min), on blood pressure, heart rate and systolic time intervals (STI’s, as a measure of positive inotropism). These results were compared with those recently published for young healthy volunteers (mean age: 26 years; Schäfers et al. 1997). Noradrenaline caused increases in systolic and diastolic blood pressure, decreases in heart rate and a shortening of STI’s that were not different from those in young volunteers. Atropine did not significantly affect these hemodynamic responses to noradrenaline, while in young volunteers it significantly enhanced noradrenaline-induced blood pressure increases and converted the heart rate decrease into an increase. In the present study in elder volunteers, tyramine caused a smaller increase in systolic blood pressure than in the previous study in young volunteers; in addition, it slightly increased diastolic blood pressure while it decreased diastolic blood pressure in young volunteers. Atropine did not significantly affect the hemodynamic effects of tyramine in the elder volunteers, while in the young volunteers it enhanced the increase in systolic blood pressure and converted the decreases in diastolic blood pressure and heart rate into increases. These results indicate a) that ageing is accompanied by a blunted baroreflex-mediated parasympathetic activation resulting in reduced cholinergic vasodilation and decreases in heart rate, and b) that ageing is associated with a decreased responsiveness of (cardiac) β-adrenoceptors and (vascular) α1-adrenoceptors which is only unmasked when the counterregulatory action of parasympathetic activation is removed.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 362-362 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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