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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Pulsatile secretion of atrial natriuretic peptide and brain natriuretic peptide in healthy humans.

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are involved in sodium and water homoeostasis in healthy humans. The plasma concentrations of the natriuretic peptides can be used to differentiate between dyspnoea of cardiac and pulmonary origin, and the degree of elevation of the peptide levels in the plasma in heart failure is a measure of the severity of the disease. However, the patterns of secretion of ANP and BNP are not clear either in healthy humans or in patients. The purpose of the present study was to test the hypotheses that both ANP and BNP are secreted in pulses in healthy humans, and that this phenomenon can be revealed by determination of ANP and BNP in peripheral venous blood samples. In 12 healthy subjects, blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 2 h. Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. Pulsatile secretion of ANP was seen in 10 out of 12 subjects [nu=0.028 min(-1) (median; range 0.013-0.047 min(-1)), i.e. a pulse of ANP with an interval of 36 min (range 21-77 min)]. Pulsatile secretion of BNP was seen in nine out of 12 patients [nu=0. 021 min(-1) (range 0.013-0.042 min(-1)), i.e. a pulse of BNP with an interval of 48 min (range 24-77 min)]. The main conclusion is that the secretion patterns of both ANP and BNP are pulsatile in most healthy humans. Consequently, it is important to study whether pulsatile secretion also occurs in heart failure in order to obtain the most informative predictive values both in the differential diagnosis of dyspnoea and in the evaluation of the severity of the disease.

Adult↗
PubMed1999

The role of nitric oxide in L-arginine-stimulated growth hormone release.

Nitric oxide (NO) exerts widespread and fundamental physiological effects. It is identical to the so-called endothelium-derived relaxing factor which regulates vascular tone. It has also been demonstrated to act as a neurotransmitter in both the peripheral and central nervous systems. NO is generated from L-arginine catalyzed by the NO synthases (NOS), of which two constitutive and one inducible form exist. NO stimulates the soluble guanylate cyclase which generates cyclic guanosine monophosphate (cGMP), that is believed to mediate the effects of NO. Recently, however, it has also been shown that NO is generated non-enzymatically from both L- and D-arginine by reaction with peroxide. The role of this pathway in the neuroregulation of growth hormone (GH) secretion has not yet been investigated. In rats, NO stimulates secretion of GH-releasing hormone (GHRH) and thus increases secretion of GH. However, it has also been observed that GHRH, in turn, increases production of NO in somatotroph cells, which subsequently blunts GH secretion. In humans, L-arginine stimulates pituitary GH release, but the mechanism is not fully clarified. Most studies suggest that an inhibition of somatostatin secretion is responsible for the effect. Infusion of low doses of the NOS inhibitor N(G)-nitro-L-arginine methyl ester have been shown not to change L-arginine-stimulated GH secretion. The effect of the NO donor molsidomine has also been found to have no influence on GH secretion. We investigated whether intravenous infusion of the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) influenced L-arginine-stimulated GH secretion in healthy young men. All subjects were examined twice in random order. On both occasions L-arginine was infused intravenously. This treatment was accompanied by either: L-NMMA co-infused or a saline infusion. Plasma cGMP was unchanged and identical in the two treatment groups, and the urine cGMP/creatinine ratio increased identically during both examinations. GH secretion increased significantly during L-arginine infusion and was not influenced by co-infusion of L-NMMA. There is so far no evidence that L-arginine stimulates GH release via NO production. However, it remains to be elucidated whether the doses of different L-arginine inhibitors/NO donors used in the previous studies were insufficient.

Animals↗
PubMed1999

The pattern of intracellular free amino acids in granulocytes from hemodialysis patients change to an oral protein supplement (granulocyte amino acids after protein in HD patients).

MATERIALS AND METHODS: The concentrations of free intracellular amino acids in granulocytes and plasma amino acids, normalized protein nitrogen appearance rate, serum insulin-like growth factors, plasma proteins, anthropometric and bioimpedance measurements were determined before and after an oral protein supplement in 19 stable patients on maintenance hemodialysis in a randomized, double-blind placebo-controlled study with crossover after 3 months. The hemodialysis patients were well-nourished with an ideal body weight of 91% after both protein supplementation and after placebo. RESULTS: After protein supplementation (7.8 g/d) the intracellular concentration of valine, isoleucine, threonine and tyrosine and the valine/glycine and tyrosine/phenylalanine ratios in the cells were significantly increased (p < 0.05). In contrast, the concentrations of plasma amino acids, serum insulin-like growth factors, and plasma proteins and body weight and anthropometric and bioimpedance measurements were unchanged. Dialysis efficiency was unchanged throughout the study. CONCLUSIONS: The present study supports the conclusion that protein supplementation to well-nourished hemodialysis patients does not improve the nutritional status measured by plasma proteins, body weight, anthropometric and bioimpedance measurements. The increase in intracellular amino acid concentrations indicates better cellular nutrition and metabolic control.

Adult↗
PubMed1999

Renal effects of brain natriuretic peptide in patients with congestive heart failure.

The effect of a continuous infusion of human brain natriuretic peptide, 2 pmol.min-1.kg-1, during 60 min was studied in nine patients with congestive heart failure and in 10 healthy control subjects. Brain natriuretic peptide increased from 1.6 to 101 pmol/l in control subjects and from 25 to 173 pmol/l in congestive heart failure during infusion. Urinary sodium excretion increased significantly in both congestive heart failure (60%) and control subjects (71%), but the absolute increase was significantly lower in congestive heart failure (27 micromol/min) than in control subjects (190 micromol/min). Urinary flow rate did not change. The lithium clearance technique was used to evaluate the segmental tubular function; the distal fractional reabsorption of sodium decreased significantly less in congestive heart failure (DFRNa: -0.8%) than in control subjects (DFRNa: -3.7%). Baseline values for glomerular filtration rate and renal plasma flow were reduced in congestive heart failure, but brain natriuretic peptide induced no significant changes between congestive heart failure and control subjects. Brain natriuretic peptide induced the same absolute increase in secondary messenger cGMP in plasma and urine in both patients and healthy subjects. It is concluded that the natriuretic response to brain natriuretic peptide infusion was impaired in patients with congestive heart failure compared with healthy subjects, and it is likely that the impaired natriuretic response was caused by a reduced responsiveness in the distal part of the nephron.

Adult↗
PubMed1998

Targeting of nucleic acid junctions: addressing to a branch point an oligodeoxynucleotide conjugated with an intercalator.

It is possible to enhance targeting of a DNA stem flank domain with a complementary DNA when it is conjugated with diphenyl ether at the branch point. The nucleoside 2'-deoxy-5-methyl- N 4-(4-phenoxyphenyl)cytidine (5) was synthesized from thymidineby tritylation, acetylation, amination via 2,4, 6-trimethylbenzenesulfonyl activation and subsequent de-protection. When a three-way junction is formed with a bulged nucleoside 5 at the branch point, the thermal melting temperature was increased by 9 degreesC when compared with wild-type DNA. When hybridizing to one of the flanks at a stem allowing coaxial stacking to the stem, modification at the branch point resulted in DeltaTm= 5.8 degreesC. For targeting to RNA the results were more ambiguous. RNase H activity was observed in some cases when an intercalating aromatic ring was addressed at the branch point. RNase H activity was observed even for a short 7mer ODN.

Base Sequence↗
PubMed1998

Synthesis and anti-HIV-1 activity of novel 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones.

Appropriately substituted 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones 9-12 and 18 were considered as annulated analogues of HEPT (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine), and some of these compounds were also found active against HIV-1, the most active one being 2,3-dihydro-5-[(3,5-dimethylphenyl)methyl]-3-ethoxy-6-ethyl-7H- thiazolo[3,2-a]pyrimidin-7-one (10b). S-Alkylation of 5-alkyl-6-(arylmethyl)-2-thiouracils 1-4 was performed with 2-bromoacetaldehyde acetals to furnish the S-[bis(alkoxy)ethyl] derivatives 5-8 and with allyl bromide to furnish S-allyl derivatives 17. The target compounds 9-12 were obtained by an N1 regioselective intramolecular cyclization reaction of silylated 5-8 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst. Treatment of the S-allyl derivatives 17 with bromine in dry methylene chloride afforded the 3-(bromomethyl) derivatives 18.

Alkylation↗
PubMed1998

Metabolism and action of urodilatin infusion in healthy volunteers.

OBJECTIVES: The objective of this investigation was to study both the pharmacokinetics and renal pharmacodynamic properties of intravenously infused urodilatin in human beings. METHODS: Twelve healthy subjects received a short-term infusion (90 minutes) of urodilatin and placebo with a graded infusion rate (from 7.5 to 15 to 30 ng.kg body weight-1.min-1) in a randomized, double-blind, crossover study design. The renal parameters were evaluated by clearance technique with the use of 51Cr-ethylenediaminetetraacetic acid, 125I-hippuran, and lithium. Urodilatin concentrations were determined by a radioimmunoassay with a urodilatin-specific antibody. RESULTS: Kinetics were characterized by a high apparent volume of distribution (43.7 +/- 11.2 L), a high total body clearance (5383 +/- 581 ml/min), and a short plasma half-life (5.57 +/- 0.8 minutes). The maximal plasma urodilatin level was 177.2 +/- 25.8 pmol/L. Less than 1% of total infused urodilatin was recovered in urine. Urodilatin significantly increased glomerular filtration rate (urodilatin, 7.0%, versus placebo, -1.9%; p < 0.05), reduced effective renal plasma flow (urodilatin, -17%, versus placebo, -3%; p < 0.01), increased fractional excretion of sodium (urodilatin, 137%, versus placebo, 27%; p < 0.05), and increased urine flow rate (urodilatin, 46%, versus placebo, -15%; p < 0.01). Fractional excretion of lithium did not change. Mean blood pressure decreased and vasoactive hormone levels remained unchanged or increased. CONCLUSION: The natriuretic and diuretic effects of urodilatin closely followed the profile of urodilatin concentration in plasma. A major part of the synthetic urodilatin was removed from circulation by a route other than filtration through the glomeruli.

Adult↗
PubMed1998

The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis.

OBJECTIVE: Desmopressin may be a useful treatment in some, but not all, patients with nocturnal enuresis. We have evaluated a relation between nocturnal urine output in patients with primary monosymptomatic nocturnal enuresis and the treatment response to synthetic vasopressin. DESIGN: Adolescent or adult enuretics and normal subjects were enrolled in the study and admitted to hospital for a 24 hour investigation of the diurnal variation in urine output, plasma vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders or non-responders. During admission the fluid intake was restricted to 25 ml/kg per day. PATIENTS: Twenty-four patients (15-37 years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24-31 years). MEASUREMENTS: Circulating levels of AVP, ANP, plasma electrolytes and plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours) together with urine volume, urine osmolality and urine electrolytes during daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and creatinine were assessed as well as urinary and fractional excretion rates of sodium and potassium. RESULTS: Controls and DDAVP non-responders had a significant decrease in urine output at night concomitant with a significant plasma AVP amplitude in peak/nadir values although both groups lacked a significant nocturnal increase in AVP. In contrast, in DDAVP responders there was no circadian variation in urine output and thus a nocturnal polyuria together with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal urine production significantly larger than the two other groups. However, the mean 24 hour AVP levels were similar in all groups. The excessive urine production at night in DDAVP responders was accompanied by nocturnal natriuresis due to an increased fractional excretion of sodium. In contrast, nocturnal antidiuresis in controls and DDAVP non-responding enuretics coincided with diminished sodium excretion. Average ANP levels were elevated in both enuretic groups compared to normals, whereas a circadian variation was detected only in the latter. CONCLUSION: It is concluded that DDAVP responsiveness is linked to the nocturnal urine production and that no pathophysiological role can be ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics. Moreover, it is suggested that an abnormal tubular handling of sodium may contribute to the nocturnal polyuria seen in DDAVP responders.

Adolescent↗
PubMed1998

Effect of nitrendipine on renal function and on hormonal parameters after intravascular iopromide.

PURPOSE: To evaluate the effect of the low-molecular nonionic radiographic contrast agent iopromide (Ultravist) on renal function, vasoactive peptides (angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic factor (ANF)), and blood pressure, and to evaluate the influence of the calcium antagonist nitrendipine on these parameters. The findings were evaluated in a prospective double-blind and placebo-controlled randomized study. MATERIAL AND METHODS: Twenty-six patients undergoing routine aortofemoral arteriography for peripheral atherosclerotic disease were treated with nitrendipine tablets (10 mg) or placebo twice daily for a week. Angiography was performed on the fifth day of medication. Efficacy variables were determined on the day before and 2 days after arteriography. The glomerular filtration rate and renal plasma flow were measured by the constant infusion technique. Renal tubular function was estimated from the clearance of lithium. Hormones were measured by radioimmunoassays. RESULTS: Arteriography with iopromide did not change renal function. No differences between the nitrendipine and placebo groups were found in renal hemodynamics, tubular sodium handling, or blood pressure. Nitrendipine changed ANF (26.1%) compared to placebo (1.5%), whereas the other hormones were not affected. CONCLUSION: The use of iopromide for angiography did not affect renal function in normotensive patients with peripheral atherosclerotic disease. Short-term treatment with nitrendipine may lower the plasma levels of ANF but it had no effect on renal function or blood pressure. Treatment with calcium antagonists prior to arteriography with iopromide is not indicated in these patients.

Adult↗
PubMed1998

The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation.

BACKGROUND: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation. METHODS: In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium. RESULTS: At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA. CONCLUSIONS: It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.

Adolescent↗
PubMed1998

Effect of BNP on renal hemodynamics, tubular function and vasoactive hormones in humans.

The effect of a continuous infusion of human brain natriuretic peptide (BNP) was studied in 48 healthy men. The study was randomized, placebo controlled, and single blind. BNP was given in doses of 1, 2, or 4 pmol.kg-1.min-1 for 60 min, and peak values of BNP in plasma were 38, 85, and 199 pmol/l, giving increments in plasma as seen in heart or renal failure. BNP infusion increased the urinary flow rate and the excretion of sodium in a dose-dependent way. The maximal effects were +65 and +156%, respectively. GFR increased and RPF decreased, the latter in a dose-dependent manner. Blood pressure, heart rate, angiotensin II, and aldosterone were all unaffected by infusion of BNP, whereas a direct inhibition of renin secretion was seen. With the use of the lithium clearance technique, we concluded that the tubular site of action is in both the proximal and distal segments, and the major effect on sodium handling is in the distal parts of the nephron.

Adult↗
PubMed1998

Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans.

Animal studies have indicated that increased nitric oxide (NO) synthesis plays a significant role in the renal adaptation to increased sodium intake. To investigate the role of NO during increased sodium intake in humans, we studied the effect of acute, systemic injection of NG-monomethyl-L-arginine (L-NMMA) on renal hemodynamics [glomerular filtration rate and renal plasma flow (GFR and RPF, respectively)], urinary sodium excretion (FENa), systemic hemodynamics [mean arterial blood pressure and heart rate (MAP and HR)], and plasma levels of several vasoactive hormones in 12 healthy subjects during high (250 mmol/day) and low (77 mmol/day) sodium intake in a crossover design. The sodium diets were administered for 5 days before the L-NMMA treatments, in randomized order, with a washout period of 9 days between each diet and L-NMMA treatment. GFR and RPF were measured using the renal clearance of 51Cr-labeled EDTA and 125I-labeled hippuran by the constant infusion technique in clearance periods of 30-min duration. Two baseline periods were obtained, after which L-NMMA was given (3 mg/kg over 10 min), and the effect of treatment was followed over the next five clearance periods. During high sodium intake, L-NMMA induced a more pronounced relative decrease in RPF (P = 0.0417, ANOVA), a more pronounced relative decrease in FENa (P = 0.0032, ANOVA), and a more pronounced relative increase in MAP (P = 0.0231, ANOVA). During low sodium intake, the effect of L-NMMA on FENa was abolished. During low sodium intake, L-NMMA induced a sustained drop in plasma renin (31 +/- 5 vs. 25 +/- 5 microU/ml, P < 0.001), which was not seen during high sodium intake. The data indicate that increased production of NO is an important part of the adaptation to increased dietary sodium intake in healthy humans, with respect to renal hemodynamics, sodium excretion, and the secretion of renin.

Adult↗
PubMed1998

Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.

Adult↗
PubMed1998

Synthesis of 3'-azolyl-2',3'-dideoxyhexose nucleosides.

1,8-Diazabicyclo[5.4.0]undec-7-ene salts of 2-methyl-4(5)-nitroimidazole or benzotriazole were obtained in crystalline form. Michael-type addition of these salts to (4S,5R)-(E)-4,6-di-O-acetyl-5-hydroxy-2-hexenal gave, after acetylation of the product, an isomeric mixture of acetylated 3-(azol-1-yl)-2,3-dideoxy-D-arabino-hexopyranosides and 3-(azol-1-yl)-2,3-dideoxy-D-ribo-hexofuranosides. Reaction of these peracetylated adducts with trimethylsilylated thymine in the presence of trimethylsilyl trifluoromethanesulfonate (TMS triflate) afforded the corresponding nucleosides which were deprotected by using methanolic ammonia. The nucleosides were found inactive against HIV-1 and HSV-1.

Antiviral Agents↗
PubMed1998

Effect of food intake on the pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated normal subjects.

OBJECTIVE: The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a synthetic analogue of vasopressin, has recently become available for clinical use. DESIGN: A randomized, single-blind, crossover study with four treatment arms. Day A, no meal + placebo; B, no meal + 400 micrograms oral desmopressin; C, standard meal + 400 micrograms oral desmopressin; D, standard meal + 400 micrograms oral desmopressin after 1.5 hours. Plasma desmopressin was measured every 15-30 minutes for 6 hours after drug intake. An intravenous hydration regimen was employed on each study day. SUBJECTS: Sixteen healthy, non-smoking, mean aged 20-35 years (mean 27.8 years). MEASUREMENTS: Plasma desmopressin concentrations were measured throughout each study day to calculate the area under the desmopressin plasma-concentration-time curve to infinity (AUCinf), the maximum plasma desmopressin concentration (Cmax), the time at which Cmax was reached (Tmax) and the time at which plasma desmopressin was first detected (Tlag). Urine volume, urine osmolality and plasma sodium concentrations were also measured at specified times on each study day. RESULTS: The total absorption of oral desmopressin, reflected by the AUCinf, was significantly higher when taken during the fasting state (day B) compared with its administration with or 1.5 hours after a standard meal (days C and D). In addition, Cmax was higher and both Tmax and Tlag were shorter on day B compared with days C and D. No effect of food ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume was decreased and urine osmolality was increased to similar extents on all active treatment days (B, C and D). No significant reductions in plasma sodium concentrations (a safety parameter) was observed during the trial. CONCLUSIONS: The gastrointestinal absorption of desmopressin is reduced and delayed if administered with or 1.5 hours after a meal. This decreased absorption of desmopressin did not have an impact on the antidiuretic action of the drug since all treatment regimens elicted a maximal response. It is possible that administration of desmopressin in the fasting state may prolong its duration of action.

Administration, Oral↗