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Biomedical subjects

H Schweer

Publications and source records attributed to H Schweer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Desmopressin effect on acetylsalicylic acid impaired platelet function.

The mechanism of DDAVP's shortening of acetylsalicylic acid (ASA) prolonged bleeding times was investigated. Sixteen healthy subjects received two dosages of ASA (100 mg) in 12 hours. Twenty four hours after the first ASA application and again after 32 hours DDAVP was administered intravenously (0.4 micrograms/kg). The trial was terminated after 48 hrs. In between, blood samples were drawn and analyzed for the in vivo bleeding time (Simplate time), in vitro bleeding test (IVBT, Thrombostat 4000), von Willebrand factor antigen (vWf:Ag), Ristocetin cofactor activity (vWf R:Co), plasma beta-thromboglobulin (beta-TG), platelet ATP/ADP, platelet aggregation (collagen, ADP, arachidonic acid), and plasma and platelet thromboxane levels. Simplate time (BT) and IVBT showed an excellent inverse correlation with vWf R:Co (r2 BT = 0.97 and r2 IVBT = 0.99, respectively) during the time when DDAVP was administered, suggesting the involvement of plasma vWF in DDAVP's shortening of the bleeding time. The involvement of plasma thromboxane in this mechanism could be excluded. In addition, DDAVP hampered platelet aggregation tests, possibly due to the inhibition of the release reaction (reduced beta-TG in plasma) by a direct interaction with platelets.

Adult↗
PubMed1995

Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy volunteers following intravenous infusion.

Prostaglandin E1 (PGE1) (30, 60, 120 micrograms) was administered by intravenous infusion over a 120 min period in an open, three way randomized, cross-over study to 12 healthy male volunteers. For the evaluation of PGE1, PGE0 and 15-keto-PGE0, blood samples were drawn prior to, during and after the infusion. Analytical measurements were performed by gas chromatography/negative ion chemical ionization triple stage quadruple mass spectrometry, a highly specific and sensitive GC/MS/MS-method. During intravenous infusion of 30, 60 and 120 micrograms PGE1, endogenous plasma PGE1 concentrations increased from 1.7 +/- 0.8 to 4.2 +/- 1.1, 6.7 +/- 1.0 and 11.0 +/- 1.9 pg ml-1 respectively. PGE0 plasma concentrations increased from endogenous levels of 1.3 +/- 1.0 pg ml-1 to 7.6 +/- 2.1, 14.1 +/- 3.7 and 28.0 +/- 3.0 pg ml-1 respectively, whilst 15-keto-PGE0 plasma concentrations increased from endogenous levels of 10.2 +/- 13.9 pg ml-1 to 99.3 +/- 27.9, 190.4 +/- 52.5 and 357.2 +/- 72.6 pg ml-1 respectively. Within the dose range of 30-120 micrograms PGE1 2 h-1 there was a linear increase of Cmax and AUC with the dose. The results of the analysis of variance after baseline and dose-correction show a 90% confidence interval in the bioequivalence acceptance range of 80 to 125%.

Adult↗
PubMed1994

Determination of seven prostanoids in 1 ml of urine by gas chromatography-negative ion chemical ionization triple stage quadrupole mass spectrometry.

In an isotope dilution assay, prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane (Tx) B2 and their metabolites PGE-M (11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3-dinor-TxB2 and 11-dehydro-TxB2 were determined in urine by gas chromatography-triple stage quadrupole mass spectrometry (GC-MS-MS). After addition of deuterated internal standards, the prostaglandins were derivatized to their methoximes and extracted with ethyl acetate-hexane. The sample was further derivatized to the pentafluorobenzylesters and purified by thin-layer chromatography (TLC). Three zones were scraped from the TLC plate. The prostanoid derivatives were converted to their trimethylsilyl ethers and the products were quantified by GC-MS-MS. In each run, two or three prostanoids were determined.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Determination of prostaglandin E1 and its main plasma metabolites 15-keto-prostaglandin E0 and prostaglandin E0 by gas chromatography/negative ion chemical ionization triple-stage quadrupole mass spectrometry.

Prostaglandin E1 (PGE1), 15-keto-PGE0 and PGE0 in plasma were determined in an isotope dilution assay by gas chromatography/triple-stage quadrupole mass spectrometry. After addition of deuterated internal standards, the prostaglandins were extracted by a solid-phase cartridge and derivatized to the pentafluorobenzyl ester methoxime. The samples were purified by thin-layer chromatography, converted to the trimethylsilyl ethers and quantified by gas chromatography/triple-stage quadrupole mass spectrometry. The parent ions in the negative ion chemical ionization mode were [M-pentafluorobenzyl]- ([P]-), the daughter ions used for quantification were [P-(CH3)3SiOH]- (PGE0 and 15-keto-PGE0) and [P-2(CH3)3SiOH]- (PGE1), respectively. Plasma concentrations in healthy subjects were at about 1-3 pg ml-1 for PGE1 and PGE0 and 2-15 pg ml-1 for 15-keto-PGE0. After infusion of 60 micrograms PGE1 in 2 h, the concentrations in plasma were 3-10 pg ml-1 for PGE1, 8-17 pg ml-1 for PGE0 and 115-205 pg ml-1 for 15-keto-PGE0.

Alprostadil↗
PubMed1994

Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects.

In a single-blind, randomized, two-way cross-over study with 12 healthy male volunteers, 60 micrograms of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg.ml-1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg.ml-1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.

Adult↗
PubMed1994

Gas chromatography/negative ion chemical ionization triple quadrupole mass spectrometric determination and pharmacokinetics of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostan oic acid in plasma.

11 alpha-Hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid (PGE-M) was determined in plasma. Analysis was performed using an isotope dilution assay and gas chromatography/triple quadrupole mass spectrometry (GC/MS/MS). Basal levels of PGE-M were 64.05 +/- 34.17 pg/ml. After infusion of 120 micrograms prostaglandin E1 (PGE1) in six subjects in 15 min, maximum levels of PGE-M of 618.6 +/- 210.3 pg/ml were reached 20-45 min after the end of infusion. 3 h after the end of the infusion, plasma levels were close to the preinfusion levels. The pharmacokinetics of PGE-M in plasma were also determined. PGE-M has a half-life of 8.96 +/- 3.53 min for formation and 31.71 +/- 6.39 min for elimination. In addition to PGE-M, PGE1, 15-keto-PGE1 and PGE0 were also determined by GC/MS/MS.

Adolescent↗
PubMed1993

Is arterial pressure a determinant of renal prostaglandin release?

The effect of changes in renal perfusion pressure (RPP) on renal prostaglandin (PG) release was investigated in conscious dogs (n = 10). PGE2, PGF2 alpha, and 6-keto-PGF1 alpha levels in renal venous and aortic plasma were measured in response to controlled reductions of RPP by an inflatable cuff implanted around the renal artery. PG plasma concentrations were determined by gas chromatography-negative ion chemical ionization mass spectrometry. At control RPP, PGE2 and PGF2 alpha concentrations in renal venous plasma were severalfold higher than in aortic plasma (PGE2, 54.2 +/- 13.4 vs. 9.3 +/- 2.7 pg/ml, P < 0.01; PGF2 alpha, 40.3 +/- 10.4 vs. 10.4 +/- 3.4 pg/ml, P < 0.01), whereas only a small secretion rate was found for 6-keto-PGF1 alpha (renal vein, 24.3 +/- 2.6 pg/ml; aorta, 17.4 +/- 3.4 pg/ml; P < 0.01). Concentrations of all three PGs in renal venous or aortic plasma did not change in response to reductions of RPP within the normal range of renal blood flow (RBF) autoregulation. The mean difference between PG release at a RPP of 70 mmHg and control was for PGE2 -7.9 pg/ml with a 95% confidence interval (CI) from -20.7 to + 5.0 pg/ml; for PGF2 alpha it was -13.7 pg/ml (95% CI -29.4 to +2.0 pg/ml); and for 6-keto-PGF1 alpha it was -0.9 pg/ml (95% CI -6.0 to +4.1 pg/ml). Reductions of RPP below the lower limit of RBF autoregulation (< 66 mmHg) had no effect on 6-keto-PGF1 alpha secretion rate but decreased secretion rates of PGE2 and PGF2 alpha (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In vivo prostanoid formation during acute renal allograft rejection.

Vasoconstriction during acute renal allograft rejection may be regulated by increased formation of vasoactive prostanoids. To address this hypothesis we investigated the biosynthesis of thromboxane (Tx)A2, a potent vasoconstrictor and platelet agonist, of prostacyclin (PGI2), a vasodilator and platelet antagonist, and of prostaglandin (PG)E2, a mediator of salt and water excretion, in nine children with 12 acute rejection episodes, prospectively during the first 7 weeks after renal transplantation. We used physicochemical analysis of stable urinary prostanoid index metabolites. Rejection crises were associated with an increase in TxB2 excretion from baseline median 9.2 (range 1.9-18.6) ng/h/1.73 m2 to 21.2 (range 10.0-133.0) ng/h/1.73 m2 (P < 0.005) during acute rejection episodes. Methylprednisolone pulse therapy resulted in a partial reduction, but not normalization of TxB2 excretion. Urinary 2,3-dinor-TxB2 was slightly stimulated during allograft rejection, urinary 11-dehydro-TxB2 did not change significantly. Renal PGI2 and PGE2 biosynthesis remained essentially unchanged. In contrast to acute graft rejection, patients with chronic graft rejection and those with stable graft function on different immunosuppressive regimens with or without cyclosporin A did not present stimulated renal TxA2 formation. Increased renal TxA2 formation in acute renal allograft rejection is likely to mediate vasoconstriction and potentiate the loss of renal blood flow and glomerular filtration rate, in the absence of an adequate response of the renoprotective prostanoids PGI2 and PGE2.

Acute Disease↗
PubMed1992

Formation of biologically active 13,14-dihydro-prostaglandin E1 during intravenous infusion of prostaglandin E1 in newborns with ductus arteriosus-dependent congenital heart disease.

Plasma concentrations of prostaglandin (PG) E1 (12-150, median 25 pg ml-1) and 13,14-dihydro-PGE1 (3-62, median 45.5 pg ml-1) were measured by gas chromatography-mass spectrometry in eight newborns with ductus arteriosus-dependent congenital heart disease during continuous intravenous infusion of PGE1. Formation of 13,14-dihydro-PGE1 was demonstrated for the first time in neonates. Since 13,14-dihydro-PGE1 has similar biological activities as the parent compound PGE1, pharmacological effects during PGE1 infusion are most likely related to both PGE1 and the generation and action of 13,14-dihydro-PGE1.

Alprostadil↗
PubMed1992

Reference intervals and developmental changes in urinary prostanoid excretion in healthy newborns, infants and children.

Urinary excretion of prostaglandins E2, F2 alpha, E-M (7 alpha-hydroxy-5, 11-diketotetranor-prosta-1, 16-dioic acid), 6-keto F1 alpha, 2,3-dinor-6-keto-F1 alpha, thromboxane B2, 2,3-dinor-thromboxane B2 and 11-dehydrothromboxane B2 was determined by gas chromatography-mass spectrometry in 83 healthy subjects aged one day to 37 years. The excretion rates of all prostanoids increased with advancing age. After correction for 1.73 m2 body surface area, only urinary excretion rates of prostaglandins E-M and 6-keto-prostaglandin F1 alpha depended on age. Reference intervals were calculated as the 10th and 90th percentiles for prostaglandins E2 (4-27 ng/h/1.73 m2), F2 alpha (23-87 ng/h/1.73 m2), 2,3-dinor-6-keto-F1 alpha (4-19 ng/h/1.73 m2), thromboxane B2 (1-21 ng/h/1.73 m2), 2,3-dinor-thromboxane B2 (8-36 ng/h/1.73 m2) and 11-dehydro-thromboxane B2 (15-87 ng/h/1.73 m2) in all subjects, and for prostaglandins E-M and 6-keto-prostaglandin F1 alpha in subjects aged 30 days or less (110-1140 ng/h/1.73 m2 and 7-23 ng/h/1.73 m2) and older than 30 days (62-482 ng/h/1.73 m2 and 2-12 ng/h/1.73 m2). High urinary excretion of prostaglandins E-M and 6-keto-F1 alpha during the newborn period and some distinct changes in urinary excretion of prostaglandin E2 and thromboxane B2 with advancing age suggest that these prostanoids might play a specific role during child development.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Increased biosynthesis of vasoactive prostanoids in Schönlein-Henoch purpura.

Schönlein-Henoch purpura (SHP) is an acute immune-mediated vasculitis characterized by infiltration of polymorphonuclear leukocytes into the vessel wall causing damage to the vascular endothelium by the release of proteolytic enzymes. The local inflammatory and thrombotic process may be regulated by increased biosynthesis of vasoactive prostanoids. We investigated the biosynthesis of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet agonist, prostacyclin (PGI2), a vasodilator and platelet antagonist, and prostaglandin E2, a mediator of inflammation, in 14 children with SHP by physicochemical analysis of index metabolites in plasma and urine. TxA2 and PGI2 biosynthesis in the systemic circulation was significantly elevated in the acute phase of the disease and correlated with the degree of clinical symptoms. Recurrent episodes of the disease were associated with phasic increases of plasma and urinary TxA2 and PGI2 metabolites. Renal TxA2 formation was highest in two patients presenting with the nephrotic syndrome and extracapillary glomerulonephritis. Prostaglandin E2 biosynthesis in the systemic circulation was increased in the acute phase of the disease. The enhanced TxA2 formation is consistent with phasic platelet activation in SHP. The increased PGI2 biosynthesis reflects endothelial cell damage and may be a response of vascular endothelium to modulate platelet-vessel wall and leukocyte-vessel wall interactions. Increased prostaglandin E2 formation, which probably derives from activated polymorphonuclear leukocytes and macrophages, is thought to be related to the inflammatory process in SHP.

Adolescent↗
PubMed1992

The role of prostanoids in pediatric diseases employing mass spectrometric techniques.

Urinary excretion rates of primary prostanoids and their metabolites are useful parameters to assess as well renal as systemic prostanoid activity under clinical conditions. Children with renal diseases with systemic involvement, such as Bartter syndrome, renal diabetes insipidus, postobstructive hydronephrosis, and acute renal allograft rejection, have exclusively elevated excretion rates of primary prostanoids. In patients with systemic diseases and additional renal involvement, such as hyperprostaglandin E syndrome and hemolytic uremic syndrome, rates of primary prostanoids and of their metabolites are elevated. In contrast, systemic vascular diseases without renal involvement, such as Henoch-Schönlein purpura and persistent pulmonary hypertension in the newborn, are associated only with increased systemic prostanoid activity indicated by elevated excretion rates of prostanoid metabolites, whereas excretion rates of primary metabolites are in the normal range.

Child↗
PubMed1991

Formation of 13,14-dihydro-prostaglandin E1 during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occlusive disease.

Formation of 13,14-dihydro-prostaglandin (PG) E1 during intravenous infusions of PGE1 in patients with peripheral arterial occlusive disease was investigated. Using both high performance liquid chromatography (h.p.l.c.) combined with radioimmunoassay and gas chromatography/triple stage quadrupole mass spectrometry (GC/MS/MS) basal levels of 13,14-dihydro-PGE1 were found to be close to or below the detection limits of the assay methods. Levels of the PGE1 metabolite increased significantly during the infusion periods and decreased after their end. Since 13,14-dihydro-PGE1, in contrast to its precursors 15-keto-PGE1 and 15-keto-13,14-dihydro-PGE1, is biologically active, its formation could contribute to the beneficial effects of PGE1 administered intravenously in patients with peripheral arterial occlusive disease.

Alprostadil↗
PubMed1990

Determination of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostan oic acid and 9 alpha,11 alpha-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoi c acid by gas chromatography/negative ion chemical ionization triple-stage quadrupole mass spectrometry.

11 alpha-Hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid (PGE-M) and 9 alpha,11 alpha-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid (PGF-M) in urine were determined in an isotope dilution assay by gas chromatography/triple-stage quadrupole mass spectrometry. After addition of the 2H7-labeled internal standard, O-methylhydroxylamine hydrochloride in acetate buffer was added either directly (PGE-M) or after standing overnight at pH 10 (PGF-M) to form the methoxime. The sample was acidified to pH 2.5 and PGE-M and PGF-M were extracted with ethyl acetate/hexane. Then the prostanoids were derivatized to the pentafluorobenzyl ester and purified by thin-layer chromatography and the trimethylsilyl ether was formed. The products were quantified by gas chromatography/triple-stage quadrupole mass spectrometry. For PGE-M, the fragment ions m/z 349 and m/z 356 (2H7 standard) (daughter ions of m/z 637 and m/z 644 (2H7 standard] were used. The results of the PGE-M assay were compared with those of an assay using the [2H3]methoxime as the internal standard. For determination of PGF-M, the daughter ions m/z 484 and m/z 491 (2H7 standard) with the parent ions m/z 682 and m/z 689 (2H7 standard) were chosen.

Deuterium↗
PubMed1990

Increased thromboxane biosynthesis in childhood hemolytic uremic syndrome.

Vascular endothelial cell damage plays a central role in the pathogenesis of the hemolytic uremic syndrome (HUS), resulting in intravascular platelet activation and thrombotic microangiopathy. A deficiency of the antiaggregatory prostacyclin (PGI2) has been postulated by experiments under ex vivo conditions. However, this observation has not been confirmed in vivo. The pathophysiological contribution of thromboxane (Tx)A2, a potent vasoconstrictor and platelet-aggregating prostanoid which is predominantly produced by platelets, has not been elucidated so far. In order to quantitate endogenous formation of TxA2 in children with HUS, plasma concentrations of the enzymatic metabolite 11-dehydro-TxB2 of TxA2 and urinary excretion rates of three major TxA2 metabolites, TxB2, 11-dehydro-TxB2 and 2,3-dinor-TxB2 were analyzed using gas chromatography/mass spectrometry. PGI2 biosynthesis was assessed by measuring urinary excretion of an index metabolite of its systemic production, 2,3-dinor-6-keto-prostaglandin (PG) F1 alpha, and an index of its renal production, 6-keto-PGF1 alpha. TxA2 biosynthesis was markedly elevated in the acute phase of HUS. This activation could be detected for a longer period of time than the presence of thrombocytopenia. Concomitantly in the acute phase, renal PGI2 formation was significantly elevated and systemic PGI2 formation was elevated in 50% of the patients. These data indicate that TxA2 formation is increased in the acute phase in patients with HUS. This enhanced biosynthesis is consistent with increased platelet activation, whereas the increased PGI2 biosynthesis reflects predominantly renal endothelial cell damage.

Child↗
PubMed1990

Increased renal biosynthesis of prostaglandin E2 and thromboxane B2 in human congenital obstructive uropathy.

Animal experiments have shown that after ureter obstruction hydronephrotic kidneys release increased amounts of prostaglandin E2 (PGE2) and thromboxane A2 (TxA2), suggesting that these prostanoids modify renal blood flow and excretory function in this model. To test the hypothesis that these mechanisms are also operative in congenital obstructive uropathy, we measured prostanoid excretion rates in 12 neonates and infants with congenital unilateral or bilateral hydronephrosis. Prostanoid determinations were performed by gas chromatography mass spectrometry. PGE2 and thromboxane B2 (TxB2) (non-enzymatic metabolite of TxA2) excretion exceeded the normal range in eight and 11 of 12 patients, respectively. Median PGE2 excretion was 22, range 4-572 ng/h/1.73 m2 (normal 3-16). Median TxB2 excretion was 22, range 3-188 ng/h/1.73 m2 (normal 3-7). No other renal prostanoids (prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha) or systemic prostanoid metabolites (PGE-M, 2,3-dinorthromboxane B2, 11-dehydro-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1 alpha) were consistently elevated. A second group of 12 neonates with congenital obstructive uropathy was followed sequentially. PGE2 and thromboxane B2 excretion rates increased even further after surgical decompression and gradually normalized during follow-up. There was a significant relationship between elevated FeNa and enhanced PGE2 and TxB2 excretion. These data suggest that endogenous renal formation of PGE2 and TxA2 is selectively stimulated in hydronephrotic kidneys in neonates and infants. PGE2 and TxA2 may be involved in modulating renal function in these infants.

Child, Preschool↗