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  • 1
    ISSN: 1432-0428
    Keywords: Hypertension ; atrial natriuretic peptide ; insulin ; salt-sensitivity ; kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the influence of salt-sensitivity on the plasma insulin and glucose response to infusion of ANP, we studied 22 men with essential hypertension, who were between 40 and 60 years old. After 1 month under normal Na+ intake (120 mmol Na+ per day), patients were randomly assigned to receive either ANP (0.04 μg · kg−1 · min−1) (n=15) or vehicle (50 ml saline) (n=7) over a 60-min period, while in the supine position. Plasma insulin and glucose were measured at time −60, 0, 20, 40, 60, 120, 180, 240 min. Ten days after ANP infusion, blood pressure sensitivity to changes in di etary salt intake was assessed according to a randomized double-blind crossover protocol. Patients were classified into two groups either salt-sensitive (n=8) or salt-resistant (n=7). Our results showed that plasma insulin and glucose did not change during ANP infusion in both groups. However, both plasma insulin (from 75.6 ± 45.1 pmol/l at 60 min to 121.2 ± 48.6 pmol/l at 240 min, p 〈0.05 vs time 0) and glucose levels (from 4.86 ± 0.73 mmol/l at 60 min to 6.56 ± 1.03 mmol/l at 240 min, p 〈0.01 vs time 0) rose after discontinuation of ANP in salt-sensitive patients, but did not change at all in salt-resistant patients. In conclusion, this randomized vehicle-controlled study demonstrates that plasma insulin and glucose levels increase in salt-sensitive hypertensive patients after the infusion of ANP. The increase of plasma insulin levels observed after ANP discontinuation, if occurring under physiologic conditions, could influence the blood pressure sensitivity to dietary Na+ intake.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Hypertension, atrial natriuretic peptide, insulin, salt-sensitivity, kidney. [Diabetologia (1994) 37: 308–312]
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the influence of salt-sensitivity on the plasma insulin and glucose response to infusion of ANP, we studied 22 men with essential hypertension, who were between 40 and 60 years old. After 1 month under normal Na+ intake (120 mmol Na+ per day), patients were randomly assigned to receive either ANP (0.04 µg·kg−1·min−1) (n =15) or vehicle (50 ml saline) (n =7) over a 60-min period, while in the supine position. Plasma insulin and glucose were measured at time –60, 0, 20, 40, 60, 120, 180, 240 min. Ten days after ANP infusion, blood pressure sensitivity to changes in dietary salt intake was assessed according to a randomized double-blind crossover protocol. Patients were classified into two groups either salt-sensitive (n =8) or salt-resistant (n =7). Our results showed that plasma insulin and glucose did not change during ANP infusion in both groups. However, both plasma insulin (from 75.6±45.1 pmol/l at 60 min to 121.2±48.6 pmol/l at 240 min, p〈0.05 vs time 0) and glucose levels (from 4.86±0.73 mmol/l at 60 min to 6.56±1.03 mmol/l at 240 min, p〈0.01 vs time 0) rose after discontinuation of ANP in salt-sensitive patients, but did not change at all in salt-resistant patients. In conclusion, this randomized vehicle-controlled study demonstrates that plasma insulin and glucose levels increase in salt-sensitive hypertensive patients after the infusion of ANP. The increase of plasma insulin levels observed after ANP discontinuation, if occurring under physiologic conditions, could influence the blood pressure sensitivity to dietary Na+ intake.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Essential hypertension ; endothelium ; endothelins ; cardiovascular risk.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Circulating endothelin-1 concentration was evaluated in 93 lean patients with essential hypertension, of whom 16 had impaired glucose tolerance and hyperlipidaemia, 25 had impaired glucose tolerance, 28 had hyperlipidaemia and 24 had no metabolic abnormalities; we also studied 22 control subjects. All groups were age- and sex-matched. Plasma endothelin-1 levels were higher (p 〈 0.05) in hypertensive patients with impaired glucose tolerance and hyperlipidaemia than in the remaining groups, and were directly correlated with fasting insulin levels (r = 0.506, p = 0.045). Therefore, circulating endothelin-1 concentrations are elevated in hypertensive patients with a high-risk profile due to the presence of metabolic abnormalities, and might favour the development of vascular damage. [Diabetologia (1997) 40: 100–102]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Adhesion molecules ; endothelium ; vascular cell adhesion molecule-1 ; oxidants.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 ± 6 years old) before and after 1 month of either oral N-acetyl-L-cysteine (1.200 mg/day) or placebo treatments, given in randomized, cross-over, double-blind fashion. Ten healthy subjects (7 men, 3 women, 52 ± 4 years old) served as control subjects. Baseline plasma VCAM-1 concentrations were higher (p = 0.007) in non-insulin-dependent diabetic patients (707.9 ± 52.5 ng/ml) than in control subjects (627.3 ± 84.6 ng/ml). Intraerythrocytic GSSG content was higher (non-insulin dependent diabetic patients: 0.618 ± 0.185 μmol/g Hb; control subjects: 0.352 ± 0.04 μmol/g Hb, p = 0.0002), whereas intraerythrocytic GSH concentrations were lower (p = 0.001) in non-insulin dependent diabetic patients (6.0 ± 0.7 μmol/g Hb) than in control subjects (7.1 ± 0.5 μmol/g Hb). The mean GSH:GSSG ratio was also lower (p = 0.0001) in the first (10.9 ± 4.5) than in the second group (20.2 ± 1.4). Circulating VCAM-1 and intraerythrocytic GSH concentrations were negatively correlated in non-insulin diabetic patients (r = 0.605, p = 0.01). Treatment with N-acetyl-L-cysteine decreased plasma VCAM-1 (p = 0.01) and intraerythrocytic GSSG (p = 0.006) but increased GSH concentrations (p = 0.04) and the GSH:GSSG ratio (p = 0.004) in non-insulin dependent diabetic patients. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes. [Diabetologia (1998) 41: 1392–1396]
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; adhesion molecules ; endothelium ; vascular cell adhesion molecule-1 ; non-insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To evaluate the effects of insulin on vascular cell adhesion molecule-1 expression by cultured human vascular endothelial cells and soluble vascular cell adhesion molecule-1 release in vivo. Methods. Human vascular endothelial cells derived from umbilical cord veins were incubated with either insulin (from 10–6 to 10–9 mol/l) or tumour necrosis factor-α (5 ng/ml) for 6 to 24 h. Plasma soluble vascular cell adhesion molecule-1 concentrations were evaluated in 12 non-insulin-dependent diabetic patients (8 men, 4 women, mean age 47.1 ± 7.7 years) and 12 healthy volunteers matched for age, sex and weight (7 men, 5 women, mean age 42.2 ± 7.2 years) before and after a 2-h euglycaemic hyperinsulinaemic clamp. Results. Transcriptional activities of nuclear factor-ϰB luciferase and vascular adhesion molecule-1 luciferase statistically significantly increased after incubation with tumour necrosis factor-α. By contrast, a slight increment of nuclear factor-ϰB luciferase (mean: 1.8 ± 0.3 fold) but not of vascular cell adhesion molecule-1 luciferase transcriptional activities were detected in cells stimulated with insulin. Soluble vascular cell adhesion molecule-1 concentrations in cell supernatants increased after tumour necrosis factor-α but not insulin stimulation. In vivo, baseline plasma soluble vascular cell adhesion molecule-1 concentrations were higher (p = 0.03) in non-insulin-dependent patients (708.7 ± 97.4 μg/l) than controls (632.1 ± 65.2 μg/l) but were not related to fasting insulin concentrations and did not change during insulin infusion. Conclusion/interpretation. The increased concentrations of circulating soluble vascular cell adhesion molecule-1 indicates that the vascular endothelium is activated in non-insulin dependent diabetic patients. Our in vitro and in vivo findings show that vascular cell adhesion molecule-1 activation cannot be due to hyperinsulinaemia. [Diabetologia (1999) 42: 1235–1239]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: An association between mixed cryoglobulinaemia (MC) and hepatotropic viruses, chiefly hepatitis C virus (HCV), has been widely reported. The presence of HCV genomic sequences or HCV-related viral proteins in the serum, purified cryoglobulins, peripheral blood mononuclear cells and into several tissues has suggested an important triggering role for HCV in MC patients. However, only few reports investigated the presence of HCV in cutaneous vasculitis and its potential pathogenetic role. Biopsies of cutaneous purpuric lesions from 5 MC female patient (aged from 40 to 80 years) were carried out for virological and histopathological evaluation. A leukocytoclastic vasculitis pattern was found in 4/5 subjects, while the presence of HCV RNA was detected in 3/5. In only 3 cases biopsy specimens were sufficient for immunohistochemical and direct immunofluorescence (DIF) studies. Immunohistochemical evaluation was performed by means of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP) immune-complexes. In the same skin specimen APAAP and DIF findings were compared with the presence/absence of HCV genomic sequences (PCR technique). In 1 MC patient, the detection of HCV-RNA was associated to a prevalent CD8+ T suppressor pattern with a perivascular and subjunctional distribution as well as an intense expresion of second class (HLA-DR) and intercellular adhesion (ICAM-1) molecules on basal keratinocytes, endothelial cells and perivascular infiltrate. These findings suggest a marked inflammatory activation that spreads from endothelial cells to keratinocytes and Langerhans cells. In the 2 HCV-RNA negative specimens the scanty immuopathological staining could indicate a residual activity due to the previous inflammatory event triggered by cryoglobulins. The deposition of circulating HCV-containing immune complexes (CIC) in the skin could be the initial pathogenic event for cryoglobulinemic vasculits; subsequently CIC could spread from vacular bed to the perivascular tissue and then could be very rapidly eliminated. If confirmed in larger patients' series these finding could definitely demonstrate a direct role of HCV in the pathogenesis of cryoglobulinemic vasculitis.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 17 (2005), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin-1β (IL-1β) is involved in hypothalamic regulation of corticotrophin-releasing hormone secretion, autonomic activation and consequent downstream modulation of the neuroimmune response. Previously, we have shown that IL-1β depolarises parvocellular neurones in the paraventricular nucleus (PVN) of the hypothalamus, and these effects are dependent on attenuation of γ-amino butyric acid (GABA)-ergic input. In the present study, using whole-cell patch clamp recordings of rat neurones in a slice preparation of the PVN, we show that the effects of IL-1β are abolished in the presence of a cyclooxygenase (COX)-2 inhibitor, NS-398, indicating a dependence on prostaglandin (PG) synthesis and activation. In response to 1 µM PGE2, 64% of parvocellular neurones tested exhibited a clear depolarisation, which was abolished in the presence of tetrodotoxin (TTX). Furthermore, neurones responsive to both IL-1β and PGE2 exhibited a decrease in the frequency of inhibitory post-synaptic potentials, suggesting that effects of these modulators are mediated via a decrease in GABA-ergic input to these neurones. A proportion (44% and 40%, respectively) of putative GABA-ergic neurones in the halo region surrounding the PVN demonstrated hyperpolarising responses to 1 nM IL-1β and 1 µM PGE2, and these effects were maintained in TTX. Furthermore, direct hyperpolarising effects of IL-1β were blocked in the presence of NS-398. Together, these data suggest that PGE2, synthesised in response to IL-1β-activation of COX-2 expressing cells, directly hyperpolarises putative GABA-ergic neurones in the halo zone surrounding and projecting to the PVN, resulting in a decrease in GABA-ergic input to parvocellular neurones and consequent depolarisation. These data further elucidate the cellular mechanisms by which IL-1β exerts its neuroimmune-related actions in the PVN.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 15 (2003), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin-1β (IL-1β) is involved in hypothalamic regulation of corticotropin releasing hormone (CRH) secretion and consequent downstream modulation of the neuroimmune response. In this study, whole-cell patch clamp recordings of rat parvocellular neurones in a slice preparation of the paraventricular nucleus (PVN) of the hypothalamus were performed to examine the cellular effects of IL-1β. In response to 1 nm IL-1β, 65% of parvocellular neurones tested exhibited a clear depolarization, which was abolished in the presence of tetrodotoxin (TTX). This depolarization was partially dependent on nitric oxide formation, as demonstrated by attenuation of the response in the presence of N-ω-nitro-l-arginine methylester, a nitric oxide synthase inhibitor. The effects of IL-1β on responsive parvocellular neurones were associated with a decrease in the frequency of inhibitory post synaptic potentials (IPSPs). Bicuculline administration blocked the effects of IL-1β, suggesting that this cytokine modulates GABA-ergic output, resulting in a decrease in inhibitory input (IPSPs) and consequent depolarization. These data support the conclusion that IL-1β influences the excitability of parvocellular neurones in the PVN, as a secondary consequence of nitric oxide generation and modulation of GABAergic inhibitory input to these cells. They elucidate cellular correlates underlying the well-established neuroimmune roles of IL-1β in the paraventricular nucleus of the hypothalamus.
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  • 10
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei einer nicht selektierten Gruppe von 45 Patienten mit gemischter Kryoglobulinämie wurde mit ELISA (Chiron ELISA HCV, Second Generation) nach Anti-HCV-Antikörpern gesucht. Die Anti-HCV-Spezifität wurde mit einem auf rekombinantem Antigen basierenden Immunoblot-Assay (Chiron RIBA HCV, Second Generation) geprüft. Die Serumproben wurden außerdem auf Marker für HBV und auf Anti-HIV-Antikörper untersucht. Zum Vergleich wurden 80 Patienten mit anderen Erkrankungen des Immunsystems auf anti-HCV getestet. Antikörper gegen HCV fanden sich bei 91% der Patienten mit gemischter Kryoglobulinämie, sie wurden in allen Fällen mit RIBA bestätigt. In der Kontrollgruppe war der HCV-Test nahezu immer negativ. Bei 49% der Patienten mit Kryoglobulinämie fanden sich auch HBV-Marker, aber in keinem Fall Antikörper gegen HIV. Die Ätiopathogenese der gemischten Kryoglobulinämie erscheint durch diese Daten in einem neuen Licht.
    Notes: Summary The prevalence of antibodies against hepatitis C virus (anti-HCV) in an unselected series of 45 mixed cryoglobulinemia patients was assessed by an enzyme linked immunosorbent assay (Chiron ELISA HCV, Second Generation). The anti-HCV specificity was evaluated by a recombinant based immunoblot assay (Chiron RIBA HCV, Second Generation Assay). HBV-related markers and HIVAb were detected in the same samples. The prevalence of anti- HCV observed in mixed cryoglobulinemia was compared with 80 patients with other immunological systemic diseases. Anti-HCV were found in 91% of mixed cryoglobulinemia patients, and confirmed by RIBA in all cases; on the other hand, anti-HCV were practically absent in other control diseases. HBV markers were recorded in 49% of mixed cryoglobulinemia subjects; while HIVAb were constantly absent. These data give us new insights into the etiopathogenesis of mixed cryoglobulinemia.
    Type of Medium: Electronic Resource
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