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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: 1432-1440
    Keywords: Aldosterone ; secretion ; distribution ; turnover ; hypertension ; Aldosteron ; Sekretion ; Verteilung ; Abbau ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 11 normotensiven Kontrollpersonen, 11 Patienten mit milder essentieller Hypertonie, 5 Patienten mit fortgeschrittener essentieller Hypertonie, 5 Patienten mit primärem Aldosteronismus und 13 Patienten mit Hypertonie in Verbindung mit Nierenarterienstenose wurde die Sekretionsrate (SR) und die metabolische Clearancerate (MCR) von Aldosteron bestimmt. Folgende Determinanten der metabolischen Clearancerate wurden zusammen mit MCR ausA,B, α, undβ, den Konstanten der3H-Aldosteronplasmakonzentration-Zeit-Funktion nach i.v. Injektion von3H-Aldosteron, berechnet: Die GeschwindigkeitskonstantenK 1 undK 2 für die Verteilung und den Abbau des Aldosterons, die virtuellen VerteilungsvoluminaV 1 undV 2, die Äquilibriumzeitt eq und die biologische Halbwertszeitt 1/2. Zusätzlich wurden die mittlere Aldosteronplasmakonzentration (mPC) und die mittlere Gesamtmenge austauschbaren Aldosterons (mmP) berechnet. SR, mPC und mmP waren leicht erhöht in den meisten Fällen von milder essentieller Hypertonie und signifikant erhöht bei fortgeschrittener essentieller Hypertonie, bei primärem Aldosteronismus und bei Hypertonie mit Nierenarterienstenose. HinsichtlichA,B,α,β,K 1,K 2,V 1,V 2,t eq ,t 1/2 und MCR war für keine der vier Gruppen von Hochdruckpatienten ein signifikanter Unterschied zur Kontrollgruppe nachzuweisen. Die Ergebnisse erlauben die Schlußfolgerung, daß die Hyperaldosteronämie mit erhöhter Gesamtmenge austauschbaren Aldosterons bei den untersuchten Hochdruckformen aus der erhöhten Aldosteronsekretion resultiert, während Verteilung und Abbau des Hormones unverändert bleiben.
    Notes: Summary The secretion rate (SR) and metabolic clearance rate (MCR) of aldosterone were assessed in 11 normotensive control subjects, in 11 patients with mild essential hypertension, in 5 showing advanced essential hypertension, in 5 with primary aldosteronism, and in 13 with hypertension associated with renal artery stenosis. The following determinants of the metabolic clearance rate were computed together with MCR fromA,B, α, andβ, the constants of the3H-aldosterone plasma concentration—time—function resulting after i.v. injection of3H-aldosterone: The rate constantsK 1 andK 2 for distribution and turnover of aldosterone, the apparent volumes of distributionV 1 andV 2, the equilibrium timet eq , and the biological half-timet 1/2. In addition, mean plasma concentration of aldosterone (mPC) and mean body pool of miscible aldosterone (mmP) were calculated. SR, mPC and mmP were slightly increased in most cases with mild essential hypertension, and significantly increased in advanced essential hypertension, in primary aldosteronism and in hypertension associated with renal artery stenosis. None of the groups of hypertensive patients differed significantly from the control group with regard toA,B, α,β,K 1,K 2,V 1,V 2,t eq ,t 1/2, and MCR. These results suggest that hyperaldosteronaemia and increased quantities of miscible aldosterone in the types of hypertension studied are due to increased aldosterone secretion, while distribution and turnover of the hormone remain unchanged.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 1209-1215 
    ISSN: 1432-1440
    Keywords: Pheochromocytoma localization ; Plasma catecholamines ; Adrenal phlebography ; Ultrasonography ; Computed tomography ; Phäochromocytomlokalisation ; Plasmakatecholamine ; Nebennierenphlebographie ; Sonographie ; Computer-Tomographie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei sechs Patienten mit adrenalem Phäochromocytom erfolgte die Lokalisationsdiagnostik durch Ultraschalluntersuchung, Phlebographie der Nebennieren und selektiver Katecholaminbestimmung im Blut der Vena cava sowie der Nebennierenvenen. Durch die selektive Katecholaminbestimmung konnten alle Phäochromocytome lokalisiert werden, durch die Ultraschalluntersuchung fünf, durch die Phlebographie vier. Ein Phäochromocytom von 1,5 g Gewicht, das nur durch die selektive Katecholaminbe-stimmung, nicht aber durch Ultraschall oder Phlebographie lokalisiert wurde, konnte computertomographisch dargestellt werden. Um Fehldiagnosen bei der selektiven Katecholaminbestimmung zu vermeiden, darf vor der Blutentnahme aus den Nebennierenvenen kein Röntgenkontrastmittel injiziert werden, da dies zu einer erheblichen Adrenalin- oder Noradrenalinfreisetzung aus dem Nebennierenmark führen kann.
    Notes: Summary In six patients with adrenal pheochromocytoma the tumors were localized by ultrasonography, phlebography of the adrenal glands and by estimation of plasma catecholamines selectively obtained from the vena cava and the adrenal gland veins. All tumors were localized by selective catecholamine estimation, five by ultrasonography, and four by phlebography. The smallest pheochromocytoma of 1.5 g weight was only localized by selective catecholamine estimation but not by ultrasonography or phlebography. This tumor, however, had been visualized by computed tomography. To avoid diagnostic errors by selective catecholamine estimation, it is important to withdraw blood from the adrenal gland veins prior to the injection of any radiographic contrast media, since this may result in an extremely enhanced secretion of catecholamines from the adrenal medulla.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Blood pressure ; Catecholamines ; Eicosapentaenoic acid ; Essential hypertension ; Intracellular free calcium ; Lipids ; Platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103±1 to 98±2 mmHg (P〈0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102±8 nM to 86±6 nM, P 〈 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinphrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension. The decrease in basal intracellular free platelet calcium concentration does not seem to be due to a diminished responsiveness of the calcium messenger system to thrombin.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 47 (1994), S. 207-208 
    ISSN: 1432-1041
    Keywords: Clarithromycin ; Macrolide antibiotics ; FK 506 ; drug interaction ; renal transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 61 (2005), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serum procalcitonin (PCT), an accurate marker of severe infection, is moderately increased in chronic kidney disease (CKD), peritoneal dialysis (PD) and haemodialysis (HD). We studied the extent of PCT elevation and factors accounting for elevated PCT in CKD and dialysis, and whether peripheral blood mononuclear cells (PBMC) contribute to increased PCT. In 37 controls, 281 CKD, 31 PD, and 65 HD patients without infection, PCT was measured and correlated with CKD stage, PD, HD, C-reactive protein (CRP), cardiovascular disease (CVD) and other clinical parameters. PCT release by PBMC from controls, advanced CKD, PD and HD patients (12 subjects each) was measured. PCT increased in parallel to the deterioration of CKD. Oliguria, advanced CKD, PD, HD, CVD and elevated CRP were independently associated with PCT elevation. PCT release from PBMC significantly increased in advanced CKD, PD and HD. PCT release from PBMC correlated closely with the corresponding serum PCT values (r = 0.76, P 〈 0.001). In the absence of infection, PCT may increase due to reduced renal elimination and increased synthesis, as due to PBMC. Furthermore, serum PCT could serve as a marker of low-grade inflammation and CVD, which substantially increase mortality in CKD and dialysis.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 337 (1974), S. 872-872 
    ISSN: 1435-2451
    Keywords: Pheochromocytoma ; Malignancy ; Phäochromocytom ; Dignitätsbestimmung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die auf das 10fache gesteigerte Katecholaminausseheidung, der Abbruch der A. coeliaca and seine Inoperabilität t ließen sin Phäochromocytom als maligns erscheinen. Eine postoperativ auftretende Transaminasenerhöhung usw. wurde als Lebermetastasierung gedeutet. Die seit 2 Jahren bestehende Spontanremission (der Patient ist als Kraftfahrzeugmechaniker wieder voll arbeitsfähig!) ließen die Malignität anzweifeln. Eine Kontrollangiographie bestätigte jedoch durch den Ausfall der rechten Niere das fortschreitende expansive Wachatum des Tumors.
    Notes: Summary An excessively high secretion of catecholamines (10 times the normal amount), the loss of the A. coeliaca, and the inoperable nature of a pheochromocytoma all seemed to indicate that the growth was malignant. Postoperative rises in the levels of transaminases etc. were interpreted as a sign of metastasis in the liver. The malignancy was later questioned due to a spontaneous clinical remission beginning two years ago (the patient is quite capable of his work as a car mechanic). Follow-up angiography confirmed progressive expansive growth of the tumor, however, as the examination revealed the loss of the right kidney.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 93 (1998), S. s051 
    ISSN: 1435-1803
    Keywords: Key words Anti-hypertensive treatment – AT1 receptor blocker – candesartan cilexetil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The main goal of the treatment of hypertension is to decrease cardiovascular morbidity and mortality. Since this has been demonstrated for betablocker and diuretics only, other antihypertensive agents should be recommended for initial single-drug therapy only if they demonstrate that their antihypertensive potency, and their tolerability is at least comparable to that of the other established drug classes. From this latter perspective AT1 blockers should become one of the most favored anti-hypertensive drugs, since it can be shown that their efficacy is comparable to all other classes of antihypertensive drugs and their tolerability is undoubtedly better. Candesartan seems to be the most efficient AT1 blocker with regard to molar potency. Moreover, it has been shown that Candesartan achieves an impressively long duration of action presumably due to its special receptor binding properties with a peak through ratio of more than 0.9. An other advantage of this special AT1 blocker may be its dose response curve which demonstrates a continuous increase of efficacy between 2 and 16 mg daily.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1041
    Keywords: Key words Cyclosporin A ; Drug monitoring; liver dysfunction ; transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Apparent cyclosporin A (CSA) blood levels, as determined by fluorescence polarization immunoassay (FPIA) and enzyme-multiplied immunoassay technique (EMIT), were compared in CSA-treated patients with various degrees of liver dysfunction. Methods: FPIA and EMIT were performed in parallel according to test manufacturer instructions in blood from kidney (n=82), liver (n=96) and heart transplant (n=20) patients. Results: The precision of both techniques was greatest in patients with the highest blood levels, and at each blood level greater for the FPIA than for the EMIT. Apparent CSA blood levels, as determined by EMIT, were typically approximately 70% of those determined by FPIA, indicating greater cross-reaction of the antibody in the FPIA with CSA metabolites. However, the ratio of values determined with EMIT and FPIA was very similar in kidney, liver and heart transplant patients. Among liver transplant patients it was also very similar in those without major alterations of hepatic function and in those with impaired excretory (increased bilirubin and γGT) or synthetic (i.e., reduced thromboplastin time) function. Extended storage of blood samples for up to 10 days did not affect apparent CSA blood level estimates by EMIT in a clinically relevant manner. Conclusions: We conclude that the greater specificity of the antibody in the EMIT for the CSA parent compound does not translate into a clinically relevant advantage for CSA monitoring.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 314-323 
    ISSN: 1432-1912
    Keywords: Noradrenaline ; Neuropeptide Y ; 1A-adrenoceptor ; Y1 NPY receptor ; Microvessel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have studied the contractile effects of the sympathetic transmitter noradrenaline and its cotransmitter neuropeptide Y (NPY) given alone and in combination on isolated rat mesenteric resistance vessels (200–300 μm diameter). Noradrenaline and NPY each concentration-dependently contracted rat mesenteric microvessels (EC50 ≈ 800 nM and 10 nM, respectively), but noradrenaline caused considerably greater maximal effects than NPY (14.3 mN vs. 3.5mN). A low antagonistic potency of yohimbine indicated that the response to noradrenaline did not involve α2-adrenoceptors, and the subtype-selective antagonists 5-methylurapidil, tamsulosin and chloroethylclonidine indicated mediation via an α1A-adrenoceptor. Shallow Schild regressions for prazosin and 5-methylurapidil indicated that an α1-adrenoceptor subtype with relatively low prazosin affinity might additionally be involved. Studies with the NPY analogues PYY, [Leu31, Pro34]NPY and NPY18–36 demonstrated that NPY acted via a Y1 NPY receptor. In addition to its direct vasoconstricting effects NPY also lowered the noradrenaline EC50 but did not appreciably affect maximal noradrenaline responses indicating possible potentiation. The potentiating NPY response occured with similar agonist potency as the direct contractile NPY effects and also via a Y1 NPY receptor. The Ca2+ entry blocker nitrendipine (300 nM) reduced direct contractile responses to noradrenaline and NPY but did not affect the potentiation response to NPY.
    Type of Medium: Electronic Resource
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