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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 145 records · Page 8Linked to original sources
PubMed1994

5'-Azido and 5'-fluoro alpha-nucleosides as analogues of AZT and FLT.

5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their corresponding alpha-anomers 11 have been synthesized by condensation of methyl 3-O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated nucleobases followed by deprotection with methanolic ammonia. Reaction of silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino-pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino-pentofuranoside (17 alpha) afforded a mixture of the alpha-nucleosides 20 and the acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1-(thymin-1-yl)-D -arabinitol (22). Compounds 20 and 22 were deprotected with methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The new nucleosides were inactive against HSV-1 and HIV-1.

Animals↗
PubMed1994

Enhanced plasma endothelin in healthy uninephrectomized subjects during basal conditions and after indomethacin.

Plasma levels of immunoreactive endothelin (ir-ET) at basal resting conditions and the effects of indomethacin (150 mg orally) on the plasma level of ir-ET and renal haemodynamics were evaluated in 14 healthy uninephrectomized subjects (Unx) and in 14 sex- and age-matched healthy controls subjects (Cs). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125iothalamate and 131I-hippuran as references substances. Immunoreactive endothelin was measured by radioimmunoassay after prior extraction. At basal resting conditions the plasma level of ir-ET was significantly higher in the Unx group. (Unx: 1.28 pmol/l versus Cs: 0.99 pmol/l, P = 0.02, medians). After indomethacin the plasma level of ir-ET increased significantly in both groups and the ir-ET level remained significantly higher in the Unx group compared with the Cs group. Both GFR and RPF decreased significantly after indomethacin (after 120 min: Unx: GFR, -10.9%; RPF, -6.7%; and Cs: GFR, -12.5%; RPF, -7.8%, medians). A negative correlation in the percentage decrease in GFR (rho = -0.58, P = 0.03) and RPF (rho = -0.61, P = 0.03) and the percentage increase in ir-ET 2 h after indomethacin was only found in the Cs group. It is concluded that healthy uninephrectomized subjects have a higher level of ir-ET than healthy controls subjects both during basal conditions and after indomethacin. Indomethacin ingestion resulted in comparable decreases in renal haemodynamics in the two groups. It is suggested that the enhanced ir-ET in uninephrectomized subjects could be due to an abnormal renal metabolism of endothelin in the remnant kidney.

Adult↗
PubMed1993

Synthesis of a carboxamide linked T*T dimer and its incorporation in oligonucleotides.

The condensation of 5'-O-protected 3'-O-(2-aminoethyl)thymidine with 1,2-dideoxy-1-thyminyl-beta-D-erythro-pentofuranuronic acid gives a T*T dimer with * representing a 3'-OCH2CH2NHC(O)-4' linkage connecting the two pentofuranosyl moieties. The incorporation of this dimer in oligonucleotide sequences show only moderately lowered Tm values when hybridized with a complementary DNA relative to the unmodified DNA duplex. Consistently, no looped-out or bubble-type structure could be detected in DNA duplexes with an internal T*T module. Moreover, the 5-atom carboxamide linker causes complete stop on DNA polymerization and on exonuclease III degradation.

Base Sequence↗
PubMed1993

The ontogeny of estrogen receptors in heterochronic hippocampal and neocortical transplants demonstrates an intrinsic developmental program.

We investigated the intrinsic vs. environmental regulation of estrogen receptor (ER) ontogeny in the neocortex, hippocampus and hypothalamus by employing a heterochronic transplantation paradigm. These studies were based on previous reports demonstrating that neural ER develop asynchronously with quantitatively distinct ontogenetic profiles in various brain regions. Fetal (E14-15) hippocampal, frontal cortical or hypothalamic preoptic area (HPOA) primordial tissue was grafted into frontal cortical lesion cavities made in newborn (PND-0) rats. Thus, the grafted tissue was 1 week younger than the host. Two and 4 weeks following transplantation surgery, which corresponds to a theoretical donor age of PND-7 and PND-21, the grafts, a region of the host neocortex surrounding the transplant, and the host hippocampus, frontal cortex or HPOA (depending on graft type) were assayed for ER content using in vitro binding assays. ER concentration in hippocampal grafts at theoretical age PND-7 were significantly higher than those found in the host (PND-14) hippocampus and in the host neocortex adjacent to the transplant. By theoretical graft age PND-21, ER concentration in hippocampal transplants had decreased to levels comparable to those found in the host. This developmental pattern is analogous to that previously reported for the in situ hippocampus. A similar profile of ER concentration corresponding to the donor age developmental timetable was observed in neocortical grafts. ER levels in HPOA grafts did not change from theoretical donor age PND-7 to PND-21, which also corresponds to the normal ontogenetic profile. These data suggest that region-specific developmental patterns of ER expression in the rat brain are specified by embryonic day 14.

Aging↗
PubMed1993

[Lupus nephritis].

Explore the source record for details and available documents.

Cyclophosphamide↗
PubMed1993

Synthesis and anti-HIV activity of 5-alkoxymethyl-3'-azido-2',3- dideoxyuridines.

Methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-furanosi de (3) was coupled with silylated 5-hydroxymethyluracil (1a) and its C1-C6 alkyl ethers 1b-g to give the corresponding protected nucleosides 4a-g which were deprotected with Bu4NF to afford 3-azido nucleosides 5a-g and 6a-g. The alpha-anomers 6f,g show moderate activity against HIV. No significant activity against HSV-1 was found for the compounds 5 and 6.

Antiviral Agents↗
PubMed1993

Immunocytochemical and electron-microscopic characterization of macrophage/microglia cells and expression of class II major histocompatibility complex in the pineal gland of the rat.

Interstitial cells in the pineal gland of the rat were characterized immunocytochemically using the monoclonal antibodies MRC OX-42 and ED1 for macrophages/microglia, and MRC OX-6, which recognizes major histocompatibility complex (MHC) class II antigen. A polyclonal antibody against GFAP was used to identify astrocytes. Cells immunopositive for OX-42 and/or ED1 were distributed throughout the gland; they extended processes primarily along the perivascular spaces and occasionally within the parenchyma of the gland. Ultrastructurally, these OX-42-positive cells were characterized by a nucleus with sparse heterochromatin and cytoplasmic vacuoles/lysosomes. Cells expressing MHC class II antigen had a distribution and morphology similar to OX-42-immunopositive cells, suggesting that pineal macrophages/microglia play a role as antigen-presenting cells. GFAP-positive astrocytes were concentrated at the proximal end of the pineal where the pineal stalk enters the gland. The occurrence of antigen-presenting cells in this circumventricular neuroendocrine gland has important functional implications as these cells may be mediators of neuroimmunomodulatory mechanisms, and involved in certain disease states such as autoimmune pinealitis.

Animals↗
PubMed1993

Effect of pinacidil on renal haemodynamics, tubular function and plasma levels of angiotensin II, aldosterone and atrial natriuretic peptide in healthy man.

The effects of pinacidil on renal haemodynamics, tubular function evaluated by the lithium clearance technique and the plasma levels of angiotensin II (Ang II), aldosterone (Aldo) and atrial natriuretic peptide (ANP) have been evaluated in 12 healthy volunteers given pinacidil 0.1 mg/kg IV in comparison with a placebo given to 13 different healthy volunteers. Pinacidil induced significant reductions in glomerular filtration rate (-5%), renal plasma flow (-12%), urine output (-35%), urinary sodium excretion (-20%), and the fractional excretion of sodium (-17%) and potassium (-29%). Lithium clearance and proximal and distal absolute and fractional reabsorption of sodium were not significantly changed. Ang II and Aldo were significantly increased (80% and 115%, respectively) and ANP was unchanged. The mean arterial blood pressure was not significantly changed by pinacidil, but the heart rate was increased (22%). It is concluded that bolus IV injection of pinacidil in healthy subjects reduced renal blood flow, urine volume and the urinary excretion of sodium and potassium, whereas segmental tubular function was unchanged. The increase in heart rate and activation of the renin-angiotensin-aldosterone system are most likely to be secondary to stimulation of the sympathetic nervous system caused by the vasodilator effect of pinacidil.

Adult↗
PubMed1993

The effect of indomethacin infusion on renal hemodynamics and on the renin-angiotensin system during unilateral ureteral obstruction of the pig.

Obstruction of the urinary tract is associated with an increase in pelvic pressure (PP) and a decline in ipsilateral renal blood flow (RBF). To investigate the influence of the renal prostaglandins on these parameters, pigs with complete unilateral ureteral obstruction (UUO) were studied under general anesthesia after administration of indomethacin 30 minutes before obstruction. Pelvic pressure increased to a maximum of 41.1 +/- 2.4 cm. H2O after 6 hours, but maximum pressure, as well as the rate of pressure increase, was significantly reduced after indomethacin. A transient but significant increase in mean aortic blood pressure was seen, together with a bilateral decrease in RBF immediately after indomethacin administration. Ipsilaterally RBF decreased by 25% from 319 +/- 21 ml. per minute to 237 +/- 16 ml. per minute and contralaterally by 23% from 300 +/- 20 ml. per minute to 231 +/- 25 ml. per minute. After 15 hours a further decline was measured in ipsilateral RBF to 136 +/- 20 ml. per minute but, on the contralateral side, RBF was only slightly reduced to 281 +/- 36 ml. per minute after 15 hours. Following indomethacin a sustained increase in ipsilateral renal vascular resistance (RVR) was observed from 37.6 +/- 3.6 mm. Hg x ml.-1 x min. x gm. to 130.5 +/- 42.3 mm. Hg x ml.-1 x min. x gm. compared with a much smaller increase from 37.4 +/- 3.2 mm. Hg x ml.-1 x min. x gm. to 55.1 +/- 9.2 mm. Hg x ml.-1 x min. x gm. in the control group. Renal secretion rate of angiotensin II was significantly reduced 2 and 6 hours after indomethacin administration on the obstructed side, and was not significantly changed on the contralateral side. It can be concluded that inhibition of prostaglandin synthesis during unilateral ureteral obstruction in pigs results in reduced pelvic pressure, renal blood flow and angiotensin II secretion rate from the affected kidney, and that renal prostaglandin synthesis plays an important role for the perfusion of the kidney during ureteral obstruction.

Analysis of Variance↗
PubMed1993

Unchanged noradrenaline reactivity and blood pressure after corrective surgery in primary hyperparathyroidism.

In order to evaluate the role of the hyperparathyroid state for blood pressure and volume homeostasis, eight patients with primary hyperparathyroidism were studied before and after corrective surgery. Neither noradrenaline induced blood pressure changes nor basal blood pressure were affected by the operation, and the values were the same as in an age- and sex-matched control group. Noradrenaline infusion induced an increase in PTH(1-84) values before (72-86 ng l-1, medians, p < 0.02), in contrast to a decrease after (28 to 19 ng l-1, p < 0.05) operation for primary hyperparathyroidism. Basal plasma atrial natriuretic peptide was lower before than after removal of adenomata (3.2 vs. 4.8 pmol l-1, medians, p < 0.02). Cyclic 3'-5'-guanosine monophosphate was not significantly changed (4.7 vs. 5.5 nmol l-1). Aldosterone was higher before than after surgery (139 vs. 71 pmol l-1, p < 0.02), whereas angiotensin II was unaltered (20 vs. 9 pmol l-1). Arginine vasopressin was higher before than after the operation (0.9 vs. 0.7 pmol l-1, p < 0.05), but urinary excretion of prostaglandin E2 was unchanged. In conclusion primary hyperparathyroidism was not associated with changes in noradrenaline reactivity or basal blood pressure despite derangements of hormones adjusting sodium and water homeostasis. It is suggested that the hormonal changes may be secondary to a relative volume depletion.

Adult↗
PubMed1993

Skeletal muscle magnesium content during cyclosporin and azathioprine treatment in renal transplant recipients.

Cyclosporin treatment is often accompanied by hypomagnesaemia and renal magnesium wasting, but it is unknown whether cyclosporin induces tissue magnesium depletion. Magnesium status is best evaluated by measurement of skeletal muscle magnesium content. The purpose of the present study was to evaluate whether skeletal muscle magnesium content was reduced during cyclosporin treatment. In two groups of renal transplant recipients treated with either cyclosporin and prednisolone (group Cy, n = 13) or azathioprine and prednisolone (group Az, n = 17) skeletal muscle content of magnesium, serum magnesium, and urinary excretion of magnesium were determined, and the relationships between skeletal muscle magnesium content, serum magnesium and urinary magnesium were analysed. Skeletal muscle magnesium content did not differ significantly between groups; 7.93 mumol/g wet weight (median) in group Cy versus 8.38 mumol/g wet weight in group Az. Serum magnesium was significantly (P < 0.01) lower in group Cy (0.71 mmol/l) than in group Az (0.82 mmol/l). The urinary excretion of magnesium did not differ between the groups. Skeletal muscle magnesium did not correlate with either serum magnesium or urinary magnesium excretion in group Cy or group Az. Thus the present study indicates that cyclosporin-treated patients are not magnesium depleted, and serum magnesium in these patients does not reflect the skeletal muscle content of magnesium.

Adolescent↗
PubMed1993

Dose-response study of atrial natriuretic peptide bolus injection in healthy man.

The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose-response study with 50 healthy subjects. Placebo or ANP 0.5, 1.0, 1.5, or 2.0 micrograms kg-1 bwt was given as an intravenous bolus injection to five different groups. GFR rose after ANP, whereas no immediate change in RPF was observed. Significant increases with no distinct additional effect of ANP doses higher than 1.0 microgram kg-1 were detected in filtration fraction, urinary flow rate and urinary excretion rate of sodium. Both proximal and distal fractional reabsorption of sodium was reduced and the effect seemed to flatten out at doses higher than 1.0 microgram kg-1. Dose-dependent increases in cyclic guanosine monophosphate in urine and plasma were found after ANP bolus injection, and the rise in both was correlated with the increase in urinary sodium excretion. ANP caused a dose-dependent decrease in blood pressure and an increase in pulse rate. Plasma concentrations of angiotensin II and arginine vasopressin did not change after ANP. In summary, we found that ANP bolus injection caused a natriuresis and diuresis in healthy man with a threshold at a dose of 1.0 microgram kg-1. No distinct further renal effects were observed with higher doses despite dose-dependent increases in urinary cGMP excretion and plasma cGMP. Inhibition of both proximal and distal tubular fractional sodium reabsorption by ANP contributed to the natriuretic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man.

A 90-min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (TcGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min-1), free water clearance (from 4.0 to 1.3 ml min-1) and ANP (from 3.3 to 2.5 pmol l-1) and a significant increase in heart rate (from 57 to 64 beats min-1), Ang II (from 11 to 18 pmol l-1), Aldo (from 189 to 308 pmol L-1) and in the tubular secretion of cGMP (TcGMP from 28.8 to 214.4 pmol min-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Elevated level of erythropoietin in congestive heart failure relationship to renal perfusion and plasma renin.

BACKGROUND: In animal experiments reduction of renal perfusion can stimulate erythropoietin production. The relationship between renal haemodynamics and erythropoietin production is unknown in congestive heart failure. OBJECTIVE: The aim was to study the relationship between serum erythropoietin and renal haemodynamics, plasma renin activity and haematocrit in patients with congestive heart failure and in healthy control subjects. PATIENTS AND METHODS: Serum erythropoietin, renal plasma flow, glomerular filtration rate and plasma renin activity were determined in 14 patients with acyanotic congestive heart failure, and 36 healthy controls. RESULTS: Serum erythropoietin was significantly elevated in congestive heart failure 26.6 U l-1 (median) compared with controls 17.0 U l-1 despite a normal haematocrit, and increased with the severity of congestive heart failure (New York Heart Association class II: 17 U l-1 [n = 4]; class III: 30 U l-1 [n = 5]; class IV: 45 U l-1 [n = 5]). Significant inverse correlations between serum erythropoietin and renal plasma flow (r = -0.60, P < 0.03), and between serum erythropoietin and glomerular filtration rate, were found in congestive heart failure but not in the control subjects. A significant positive correlation (r = 0.71, P < 0.03) was demonstrated between serum erythropoietin and plasma renin activity in congestive heart failure. CONCLUSION: A severe reduction in renal perfusion in congestive heart failure appears to cause an increase in serum erythropoietin.

Adult↗