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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 163 records · Page 9Linked to original sources
PubMed1993

Effect of captopril on the renal veno-arterial gradient of erythropoietin and oxygen in unilateral renal artery disease.

Twenty-nine patients with unilateral renal artery stenosis or occlusion were investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO), haemoglobin oxygen saturation and plasma renin activity (PRA) was determined separately in each kidney before and 1 h after angiotensin converting enzyme inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen saturation were the same in the affected and unaffected kidney during basal conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the affected side but not on the unaffected side. A fall in s-EPO after ACE inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p < 0.01), in the contralateral vein (-0.8 U l-1, p < 0.01) and in the aorta (-0.6 U l-1, p < 0.01). The O2-gradients were reduced on both sides after captopril, from 10.8-7.5% (p < 0.04) on the affected side and from 10.8-9.0% (p < 0.04) on the contralateral. It is suggested that the stimulated renin-angiotensin system may be important for EPO production in the affected kidney in unilateral renal disease.

Adult↗
PubMed1993

Effect of captopril on renal extraction of renin, angiotensin II, atrial natriuretic peptide and vasopressin, and renal vein renin ratio in patients with arterial hypertension and unilateral renal artery disease.

Plasma renin activity (PRA) and plasma concentrations of angiotensin II (AngII), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were determined in the abdominal aorta and the renal veins before and 1 h after peroral ingestion of captopril 25 mg in 29 patients with arterial hypertension and unilateral renal artery stenosis or occlusion, in order to study the effect of ACE inhibition on single-kidney extraction ratio (ER) of PRA, AngII, ANP, and AVP, and on renal vein renin ratio (RVRR). PRA was increased, AngII and ANP were reduced, and AVP unchanged after captopril. On the affected side the negative ER or PRA (-1.03) and AngII (-0.28) and the positive ER of ANP (0.25) and AVP (0.14) were not significantly changed by captopril. On the non-affected side ER of AngII and ER of ANP were significantly reduced (ER of AngII, 0.41-0.00, ER of ANP, 0.29-0.17), but ER of PRA and ER of AVP were unchanged. RVRR was not significantly changed by captopril. RVRR was greater than 1.5 in 79% of the patients before captopril, in 82% after captopril, and in 93% either before or after captopril. It is concluded that captopril reduces ER of AngII and ER of ANP on the non-affected side but not on the affected side in unilateral renal artery disease with hypertension, and that the use of RVRR both before and after captopril improves the predictive value of RVRR with regard to the diagnosis of unilateral renal artery disease.

Adult↗
PubMed1993

Long-term graft survival after conversion from cyclosporin to azathioprine 1 year after renal transplantation. A prospective, randomized study from 1 to 6 years after transplantation.

Cyclosporin has improved graft survival after renal transplantation, but cyclosporin nephrotoxicity is a severe clinical problem. Conversion from cyclosporin to azathioprine 1 year after transplantation might improve long-term graft survival by avoidance of cyclosporin nephrotoxicity. After treatment with cyclosporin and prednisolone during the first year after renal transplantation, 106 patients were consecutively randomized to treatment with either azathioprine and prednisolone or cyclosporin and prednisolone in a prospective, controlled study during the following 5 years, i.e. 6 years after transplantation. Actuarial estimates of graft survival rates after inclusion in the study were obtained by the product-limit method of Kaplan-Meier, and the Mantel-Cox log rank test was used to compare the two treatment regimens. When the end-points in the analyses were cessation of graft function or withdrawal of immunosuppressive treatment due to side-effects, and when patients alive with graft function or who had died with a functioning graft were treated as censored observations, graft survival 5 years after inclusion in the study was 57.7 +/- 5.2% in the total material and was the same in both the azathioprine group (52.4 +/- 7.7%) and the cyclosporin group (63.3 +/- 6.7%) (log rank = 0.40, P = 0.53). When cessation of graft function was the only end-point, graft survival 5 years after inclusion in the study was 73.7 +/- 5.2% for the total material with no significant differences between the two groups (log rank = 0.58, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Synthesis of pyranoid analogues of the anti-HIV active 3'-deoxy-2',3'-didehydrothymidine (D4T).

The primary hydroxy group of ethyl 2,3-dideoxy-alpha-D-erythro-hex-2-enopyranoside (1) was selectively protected and the secondary hydroxy group was deoxygenated via the dithiocarbonate 3 from which ethyl 6-O-(4-methoxybenzoyl)-2,3,4-trideoxy-alpha-D-glycero-hex-2-eno pyranoside (4) and its regioisomer (5) were produced. These were converted into didehydro nucleosides by glycosylation of silylated heterocyclic bases in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst. The configurations of the anomeric products were assigned by 1H-NMR analysis of the corresponding saturated compounds which were obtained by hydrogenation of the double bond in the carbohydrate moiety. The compounds 9a,b,d, 10a,b, 14a,b,e,f, and 15a,b,e,f did not show any significant activity against HIV or HSV-1.

Animals↗
PubMed1992

Synthesis of 3'-alkylthio-2',3'-dideoxy nucleosides with potential anti-HIV activity from 2-deoxy-D-ribose, using a phosphorus pentoxide reagent.

Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1.

Antiviral Agents↗
PubMed1992

Human pharmacokinetics of an analogue of atrial natriuretic factor.

The pharmacokinetics of ANP-270, a 26 amino acid analogue of alpha human natriuretic factor (alpha-hANF) with a prolonged effect on isolated arterial preparations, has been studied in 40 healthy males, in a double-blind placebo controlled investigation. Placebo or ANP-270 0.3, 1.5 or 3.0 micrograms/kg were given by intravenous bolus injection, each to groups of 10 subjects. Blood samples were assayed for ANP-270 by a specific sandwich ELISA. The disappearance of ANP-270 from plasma followed a two-compartment decay, with mean distribution and elimination half-lives of 2.6 min (n = 30) and 10.6 min (n = 20), respectively. These estimates were similar to those obtained by other investigators for alpha-hANF. Their brevity explains the lack of a prolonged effect of ANP-270 in vivo compared to alpha-hANF.

Adult↗
PubMed1992

Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control.

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intraindividual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 +/- 8 years, duration of diabetes 9 +/- 5 years, mean arterial blood pressure 90 +/- 5 mmHg (means +/- SD), urinary albumin excretion rate 5.4 x/divided by 1.6 micrograms/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [125I]-iothalamate and 131I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control. 2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (sigma = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002]. 3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R2 = 0.36, analysis of variance: P = 0.009). 4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Angiotensin-converting enzyme inhibitor renography in the diagnosis of renovascular hypertension. Studies before and after angioplasty.

Renography with [99mTc] diethylenetriaminepenta-acetate (DTPA) was performed in 26 patients with renal artery stenosis (RAS), unilateral in 15 and bilateral in 11, and in 16 patients with essential hypertension with a normal renal angiogram. Nine of the patients with unilateral RAS were restudied after a successful percutaneous transluminal renal angioplasty (PTRA), i.e. complete removal of the stenosis and a normalization of the blood pressure without antihypertensive treatment. Single-kidney [99mTc]-DTPA clearance and parenchymal mean transit time (MTT) were determined at each examination. All patients were studied on two different days using the same procedure except that captopril 25 mg was given orally before renography at the second examination. In unilateral RAS captopril reduced single-kidney [99mTc]-DTPA clearance significantly on the affected side (-42.7%, median) but not on the unaffected side (-3.2%). In bilateral RAS single-kidney [99mTc]-DTPA clearance was reduced to the greatest extent on the most affected side (-43.0%) compared with the least affected side (-17.2%). In essential hypertension no significant changes were recorded on any side (-1.5% for both). After PTRA, single-kidney [99mTc]-DTPA clearance was not significantly changed by captopril either on the previously affected side (4.3%) or on the unaffected side. MTT was significantly prolonged after captopril on the affected side in unilateral RAS and on the most affected side in bilateral RAS, whereas no significant changes were found on the unaffected side in unilateral RAS, on the least affected side in bilateral RAS, or on any side in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhanced intrarenal angiotensin II generation in response to obstruction of the pig ureter.

The effect of acute unilateral complete ureteral obstruction (UUO) on renal hemodynamics has been examined in a pig model. Pigs were operated on under general anesthesia, electromagnetic flow probes were inserted around renal arteries, and catheters were implanted in renal veins and aorta for blood sampling. The influence of 15 h of obstruction on the physiological variation in immunoreactive angiotensin II (ANG II) was measured together with detailed analysis of the renal handling of ANG II in anesthetized animals. Pelvic pressure rose significantly within 2 h to a maximum of 59.9 +/- 2.9 cmH2O (n = 10). The ipsilateral renal blood flow (RBF) was reduced by 30% from 319 +/- 35 to 241 +/- 42 ml/min (P = 0.001), whereas contralateral RBF did not change. A temporary significant increase in mean aortic blood pressure was seen during the first 2 h after UUO. Renal vascular resistance increased by 44% in the obstructed kidney from 37 +/- 3 to 55 +/- 9 mmHg.ml-1.min.g during the course of obstruction. Concomitantly, the plasma concentration of immunoreactive ANG II increased from all three sample sites by 8-15 times. This increase was highly significant compared with the sham-operated group. The results show that the pig kidney responds to UUO by a net secretion of ANG II from the ipsilateral kidney. Our observations on the ANG II renal secretion rate suggest that part of the immunoreactive ANG II in the renal venous effluent originated de novo from intrarenal generation.

Angiotensin II↗
PubMed1992

Enhanced urinary excretion of albumin in congestive heart failure: effect of ACE-inhibition.

Urinary excretion of albumin and beta 2-microglobulin were measured in 13 patients with congestive heart failure, NYHA class II-IV, before and after captopril treatment for 4 weeks, and in 13 healthy control subjects. The urinary excretion of albumin was enhanced in heart failure patients compared to control subjects (12.0 micrograms min-1 vs 2.8 micrograms min-1; medians, p less than 0.01), whereas beta 2-microglobulin excretion was normal. No significant change in urinary excretion of albumin was observed after captopril. Using Spearmann's test the urinary excretion of albumin was correlated to the NYHA class (Px = 0.681, p less than 0.05, plasma renin (Px = 0.886, p less than 0.01) and plasma angiotensin II (Px = 0.5840, p less than 0.05). Correlations with atrial natriuretic peptide (rho = 0.412, p = 0.153) and aldosterone (Px = 0.487, p = 0.106) did not reach significance. By multiple linear regression analysis only plasma renin activity was correlated to albumin excretion. In conclusion, patients with congestive heart failure had an increased urinary excretion of albumin. It is suggested that the enhanced transglomerular passage of albumin in congestive heart failure is partly due to an increased intra-renal angiotensin II generation, but elevated plasma level of atrial natriuretic peptide and increased renal venous pressure may also be important pathogenetic factors.

Adult↗
PubMed1992

Atrial natriuretic peptide and parathyroid hormone (1-84) in relation to noradrenaline induced changes in blood pressure in uraemic and healthy subjects.

In order to evaluate the hormonal regulation of blood pressure (BP) in uraemia 12 patients on chronic maintenance dialysis and 14 healthy controls were studied. BP and plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), and intact parathyroid hormone (PTH(1-84)) were determined before, during, and after a 60 min noradrenaline infusion 0.1 micrograms kg-1 body wt. min-1. Mean BP increased to the same extent in the uraemic patients (median 15 mmHg, range 6-25 mmHg) as in the controls (12 mmHg, 5-25 mmHg). ANP increased during noradrenaline infusion both in patients (7.2 to 8.3 pmol/l, medians, p < 0.01) and in controls (4.4 to 6.0 pmol/l, p < 0.01), and so did cGMP (patients: 31.6 to 35.9 nmol/l, p < 0.05; controls: 6.6 to 8.7 nmol/l, p < 0.01). PTH(1-84) was higher in the uraemic patients than in the controls, but was unchanged during noradrenaline infusion in both groups. Correlation analyses gave no evidence of a direct relation between BP and ANP, but basal PTH(1-84) was negatively correlated to basal mean BP in the patients (rho = -0.615, p < 0.05), but not in the controls. In conclusion, noradrenaline induced similar elevations of BP in dialysis patients as in healthy controls despite elevated ANP and PTH(1-84) in the patients, and ANP release was stimulated in both groups. PTH(1-84) may participate in blood pressure regulation in uraemic patients.

Adult↗
PubMed1992

The impact of total unilateral ureteral obstruction on intrarenal angiotensin II production in the polycalyceal pig kidney.

Nine pigs with unilateral complete ureteral obstruction were investigated for 15 hours. Obstruction of the ureter resulted in a maximum intrapelvic pressure of 60 cmH2O within the first hour after obstruction, and a gradual decline to 40 cmH2O during the next 15 hours. In 6 pigs both renal veins were catheterized together with the abdominal aorta allowing measurement of the hormonal difference over the kidney. Plasma angiotensin II, plasma vasopressin and plasma atrial natriuretic peptide concentrations were determined. Arterial concentration of plasma angiotensin II gradually increased from 38.7 pg/ml to 252.3 pg/ml. The highest concentrations of angiotensin II were found from the ipsilateral renal vein. From 1 hour after obstruction and onward there was a negative extraction ratio of angiotensin II from the ipsilateral kidney indicating enhanced intrarenal generation of angiotensin II. No difference in vasopressin was found among the sample sites, but a significant reduction in vasopressin from 15.2 pg/ml to 4.9 pg/ml was found from the ipsilateral renal vein during the 15 hours of unilateral ureteral obstruction. Arterial atrial natriuretic peptide concentrations were higher than renal venous levels at all times. Glomerular filtration was immediately reduced to 58%. It is suggested that an increased ipsilateral generation of intrarenal angiotensin II is at least partly responsible for some of the changes in kidney function during acute obstruction.

Angiotensin II↗
PubMed1992

Synthesis of 5-alkoxymethyl derivatives of 3'-amino-2',3'-dideoxyuridine and evaluation of their activity against HIV and cancer.

5-Alkoxymethyluracils 2a-c have been prepared by acid-catalyzed etherification of 5-hydroxymethyluracil (1). Compounds 1, 2a-c, 5-methoxymethyl- and 5-benzyloxymethyl-uracil were silylated and coupled with 1,5-di-O-acetyl-3-phthalimido-2,3-dideoxy-beta- D-erythro-pentofuranose (3), in the presence of trimethylsilyl triflate as a catalyst, to give the corresponding 3'-phthalimido-2',3'-dideoxynucleosides 5a-f and 6 which on treatment with 33% methylamine-ethanol afforded the corresponding 3'-amino-2',3'-dideoxynucleosides 7a-f and 8 in high yields. Compound 7d showed colony inhibition when tested against human epidermoid cervical cancer cells. Nucleosides 5a-e, 7a-f and 8 did not show any significant activity against HIV-1.

Antineoplastic Agents↗
PubMed1992

Synthesis of 5-homologous AZT and D4T derivatives.

The 3'-iodonucleosides 4 have been synthesized by condensation of silylated 5-alkyluracils 2 with methyl 5-O-tert-butyldiphenylsilyl-2,3-dideoxy-3-iodo-D-threo-pentofur anoside (3). 4 was treated with sodium azide and the deprotected nucleoside 5 was subsequently obtained by treatment with tetrabutylammonium fluoride. The nucleoside 4 produced the corresponding 2',3'-didehydro-2',3'-dideoxy nucleoside 6 and 3',4'-didehydro-2',3'-dideoxy nucleoside 7 in elimination reactions on treatment with sodium methoxide.

Antiviral Agents↗
PubMed1992

Effect of felodipine on renal haemodynamics and tubular sodium handling in cyclosporin-treated renal transplant recipients.

The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was investigated in 10 cyclosporin-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporin in a randomised, single-blind cross-over study. Renal plasma flow (RPF), glomerular filtration rate (GFR), renal tubular sodium and water handling as judged by the lithium clearance technique, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF), and arginine vasopressin (AVP) were measured. Both RPF and GFR increased after felodipine (mean increase: RPF, 38.7%; GFR, 16.2%; P less than 0.01 for both) in spite of a significant decrease in both systolic and diastolic blood pressure (mean decrease 10.6% and 16.0% respectively, P less than 0.02 for both). Estimated by the lithium clearance technique felodipine induced a decrease in fractional reabsorption in the proximal tubules (mean 72.0% vs 63.0%, P less than 0.01), an increase in proximal output of fluid (mean 11.0 ml/min vs 16.0 ml/min, P less than 0.01), and a decrease in distal fractional reabsorption of sodium (mean 90.5% vs 83.9%, P less than 0.05) resulting in a significant natriuresis and diuresis. Ang II, Aldo, ANF, or AVP did not change. Intravenous infusion of cyclosporin per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporin treated renal transplant recipients has beneficial effects on blood pressure, renal haemodynamics, and renal tubular sodium and water handling, which seems to compensate for some of the adverse effects of cyclosporin. It is suggested that these effects result from a direct vasodilatation and an effect on proximal tubular function.

Adult↗
PubMed1992

Tubular handling of amino acids after intravenous infusion of amino acids in healthy humans.

To examine the fractional excretion of amino acids after an increase in the filtered load, and to study a possible coupling between proximal tubular reabsorption of individual amino acids and sodium/water, eleven healthy subjects were examined before and during intravenous infusion of a mixture of essential and non-essential amino acids. Thirteen healthy subjects, who received isotonic glucose instead, participated in an identical time-control study. Glomerular filtration rate (GFR), renal plasma flow (RPF), and proximal and distal absolute and fractional tubular reabsorption of sodium and water (PARNa, PFRNa/water, DARNa, and DFRNa) evaluated by the lithium clearance method were determined during four clearance periods of 30 min each. After amino acid infusion, GFR and RPF increased, whereas filtration fraction (FF) was unchanged. PARNa was unchanged, but lithium clearance increased significantly (P less than 0.05) and PFRNa/water fell, indicating an increased delivery of sodium and water out of the proximal tubules. DARNa increased, but DFRNa was unchanged, thus no net increase was recorded in urinary sodium and water output. In the time-control study, no changes in kidney function were seen. Absolute excretion of amino acids increased for glutamic acid, serine, glutamine, glycine, threonine, histidine, alanine, arginine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, and lysine (P less than 0.01), and fractional excretion increased for all but glutamic acid, tyrosine, arginine, isoleucine, and leucine. Reabsorption of amino acids was enhanced uniformly and almost paralleled the filtered load without any sign of saturation of the reabsorption mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗