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Biomedical subjects

B Scherer

Publications and source records attributed to B Scherer.

At least 37 records · Page 2Linked to original sources
PubMed1983

Prostacyclin metabolism in adults and neonates. Urinary profiles of 6-ketoprostaglandin F1 alpha and 2,3-dinor-6-ketoprostaglandin F1 alpha studied by gas chromatography-mass spectrometry.

Metabolism of endogenous prostacyclin was studied in adults and neonates by measuring urinary levels of 6-ketoprostaglandin F1 alpha (spontaneous hydrolysis product) and 2,3-dinor-6-ketoprostaglandin F1 alpha (enzymatically formed by beta-oxidation). Quantification of prostanoids was achieved by capillary gas chromatography-mass spectrometry using the stable isotope dilution technique. Purification of the urinary lipid extract included silicic acid column chromatography and reverse- and straight-phase high-pressure liquid chromatographies. Accuracy of the method was proven by recovery experiments for both metabolites. Partial mass spectra of endogenous 6-ketoprostaglandin F1 alpha and 2,3-dinor-6-ketoprostaglandin F1 alpha were obtained from urine samples. In neonates (third day of life, n - 5 pooled urines) levels of 2,3-dinor-6-ketoprostaglandin F1 alpha (0.28 +/- 0.18 ng/ml) were much lower than those of 6-ketoprostaglandin F1 alpha (2.13 +/- 1.10 ng/ml), indicating low beta-oxidation activity at high prostacyclin formation. In adults (n = 7), levels of 2,3-dinor-6-ketoprostaglandin F1 alpha (0.27 +/- 0.21 ng/ml) and levels of 6-ketoprostaglandin F1 alpha (0.20 +/- 0.11 ng/ml) were about the same, indicating relatively high beta-oxidation at low prostacyclin formation. Values are expressed as mean +/- S.D.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Arachidonic acid metabolites, hypertension and arteriosclerosis.

The level of arterial blood pressure is set by complete interactions of several mechanisms which influence both blood flow in and resistance of the vascular system. An imbalance favouring elevation of vascular resistance or extracellular volume will result in hypertension. Such alterations may include increased activity of the sympathetic nervous system, of the renin-angiotensin system, or excessive secretion of mineralocorticoids. Of equal importance may be a reduced activity of blood pressure-lowering factors such as prostaglandins and the kallikrein-kinin system. This paper describes the possible significance of prostaglandins in the pathophysiology of hypertension and in degenerative vascular disease, based on their involvement in the control of vascular resistance, renal regulation of extracellular volume and platelet-vessel wall interactions. An abnormality in the biosyn-thesis of certain prostaglandin endoperoxide metabolites may lead to hypertension even without an increase in the activity of the classic blood-pressure-elevating systems. The contribution of prostaglandins for the development of hypertension and degenerative vascular disease may be based on an inherent abnormality of the prostaglandin system, as well as on the effects of major risk factors such as dietary intake of sodium and fat on prostaglandin synthesis. Specific blockade or stimulation of distinct biosynthetic pathways leading to antagonistically acting prostaglandins and nutritional manipulation of precursor fatty acids should lead to a better understanding of the pathomechanisms involved and may offer new strategies for therapy or prevention of these cardiovascular disorders.

Arachidonic Acids↗
PubMed1982

Prostacyclin metabolites, in urine or adults and neonates, studied by gas chromatography-mass spectrometry and radioimmunoassay.

Endogenous levels of two metabolites of prostacyclin, 6-keto-prostaglandin F1 alpha (spontaneous hydrolysis product) and 6,15-diketo-13,14-dihydroprostaglandin F1 alpha (enzymatic degradation product) were measured in urine of adults and neonates by gas chromatography-mass spectrometry, using deuterated internal standards. The method comprised extraction of prostanoids by reverse-phase cartridges and purification by silicic acid column chromatography and reverse-and straight -phase high-performance liquid chromatographies. Exogenous 6-keto-prostaglandin F1 alpha and 6,15-diketo-13,14-dihydroprostaglandin F1 alpha added to urine were recovered quantitatively by gas chromatography-mass spectrometry. Endogenous levels of 6-keto-prostaglandin F1 alpha in urine of adults were 0.11 +/- 0.05 (S.D.) ng/ml (n = 12), whereas in urine of neonates the levels were much higher: 1.41 +/- 0.36 (S.D.) ng/ml (n = 5) on the 3rd day of life declining to 0.51 +/- 0.21 (S.D.) ng/ml (n = 5) on the 5th day. 6-keto-prostaglandin F1 alpha was also estimated in both age groups by radioimmunoassay. Urinary levels of 6,15-diketo-13, 14-dihydroprostaglandin F1 alpha in neonates on the 3rd day of life were 2.12 +/- 0.70 (S.D.) ng/ml (n = 4) and declined until the 5th day. In adult urine this metabolite was below the limit of detection (0.20 ng/ml).

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Analysis of 6-keto-prostaglandin F1 alpha in human urine: age-specific differences.

A radioimmunoassay (RIA) for the estimation of 6-keto-PGF1 alpha in human urine is described in detail. The RIA method was validated by direct comparison to gas chromatography-mass spectrometry. In adults and in one year old children basal excretion of 6-keto-PGF1 alpha was found to be lower than that reported for PGE2 or PGF2 alpha. However, during the first week of life, significantly more 6-keto-PGF1 alpha was excreted. The very high levels of 6-keto-PGF in urine seen on the third day of life seemed already to decrease during the first week of life. It is concluded that prostacyclin may have a major role for kidney function in the newborn, possibly by protecting the immature kidney from high levels of angiotensin II.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Acute haemodynamic and hormonal effects of captopril are diminished by indomethacin.

1. The acute haemodynamic and hormonal effects of 100 mg of captopril (SQ 14.225) orally were tested in twelve healthy men in the sodium replete state before and after indomethacin pretreatment. 2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P less than 0.02). Heart rate did not change during the whole experiment. Although plasma renin activity (PRA) increased (P less than 0.002), plasma and urinary aldosterone and plasma 18-hydroxycorticosterone (18-OH-B) decreased after captopril (P less than 0.02). Prostaglandin (PG) E2, sodium and potassium excretion rates remained constant after captopril. 3. Under indomethacin pretreatment, the fall in mean arterial blood pressure was less than without indomethacin at 30 and 60 min after captopril (P less than 0.05). Heart rate was constantly lower than without indomethacin during the whole experiment (P less than 0.05). Indomethacin pretreatment decreased basal PGE2 excretion (P less than 0.02) and baseline PRA as well as the increase in PRA after captopril (P less than 0.05). Control mineralocorticoid levels were significantly lower than without indomethacin. In indomethacin-pretreated subjects, aldosterone did not further decrease after captopril, and 18-OH-B fell only slightly. 4. Without indomethacin pretreatment a significant, positive correlation was found between PRA values before captopril and the maximum decrease of mean arterial blood pressure after captopril. Under indomethacin pretreatment this correlation was no longer demonstrable. The results suggest that prostaglandins may contribute to the haemodynamic and hormonal actions of captopril.

18-Hydroxycorticosterone↗
PubMed1982

Diverse effects: augmentation, inhibition, and non-efficacy of 12-O-tetradecanoylphorbol-13-acetate (TPA) on retrovirus genome expression in vivo and in vitro.

The action of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several retrovirus-related functions was investigated in four virus-host cell systems. The following effects were recorded: (i) in STU-mice, infected with the Friend virus complex (Friend) murine leukaemia virus/Friend spleen focus forming virus) and treated with TPA (50 ng/g) for one week prior to infection, the number of spleen foci increased 5-fold over the control. (ii) Addition of TPA (0.04 to 40 ng/ml) to virus-producing cell systems resulted in a 2-fold increase of extracellular reverse transcriptase activity. The maximum response was observed in Friend leukemia virus-producing mouse cells at 0.1 to 0.4 ng TPA/ml and in simian sarcoma virus-producing rat cells at 4 ng/ml. (iii) The efficiency of transformation of BalbC 3T3 cells by Moloney murine sarcoma virus, tested in a focus formation assay, was slightly enhanced by TPA. (iv) TPA inhibited the induction of endogenous virus formation in B cell mitogen-stimulated spleen cell cultures from BalbC mice.

Animals↗
PubMed1982

Studies on the mechanism by which ACTH stimulates renin activity and angiotensin II formation in man.

Ten IU of ACTH (1-24) per day was infused for 34 h (starting at 7 a.m.) into 8 normal men on a constant diet containing 135 mM Na+ per day. All subjects retained between 152 and 181 mM of sodium. Potassium balance was negative. Plasma renin activity (PRA) and plasmaangiotensin II (P-A-II) started to rise in most subjects after 6 to 8 h of infusion, reached a maximum after 24 h and then tended to decline. As shown previously, the rise in PRA is not due to a rise in plasma renin substrate concentration. Systolic, but not diastolic blood pressure increased significantly on the second day of ACTH-infusion. Plasma cortisol (P-F) was continuously stimulated by ACTH. Plasma aldosterone (P-aldo) increased rapidly 1 h after ACTH administration, then tended to fall, and increased again in most subjects, roughly in parallel with PRA. No significant changes in electrolyte balance, PRA, P-A II, P-F, and P-aldo occurred in 3 subjects receiving 'sham' infusions. Additional experiments in subjects treated with propranolol or indomethacin allowed the conclusion that the effect of ACTH on PRA and P-A II is not mediated by renal beta-adrenergic receptors, but perhaps (partially?) by prostaglandins. Since the infusion rate of ACTH was not much higher than the secretion rate of ACTH in the early morning hours, it is possible that ACTH is physiologically involved in the regulation of renin secretion.

Adrenocorticotropic Hormone↗
PubMed1981

ACTH stimulates plasma renin and angiotensin II in man.

1. Adrenocorticotropic hormone (ACTH; 10 i.u./day) was infused for 34 h into normal male subjects. Some subjects were additionally treated with propranolol or indomethacin. Others received sham infusions or hydrocortisone infusions instead of ACTH. 2. ACTH, but not sham or hydrocortisone infusions, led to a significant increase in plasma renin activity and angiotensin II concentration with a lag period of 7--10 h and a maximum response after 24 h. ACTH may be a physiological regulator of renin secretion, perhaps through a 'trophic' effect on the juxtaglomerular apparatus. 3. The effect of ACTH on renin is not mediated by a rise in plasma renin substrate, probably not by renal beta-adrenoreceptors, but perhaps by prostaglandins. 4. A dissociation between plasma cortisol and aldosterone during ACTH infusion suggests that ACTH, in this dosage, stimulates aldosterone on the second day through renin and angiotensin II, before its secretion is finally suppressed during more prolonged infusion.

Adrenocorticotropic Hormone↗
PubMed1980

Renal factors in juvenile hypertension.

Essential hypertension in infancy, one believed to occur rarely if ever, is now increasingly recognized as a potential precursor of essential hypertension in adulthood. The mechanisms responsible for hypertension in childhood and adolescence are only beginning to be delineated. Renal factors assumed to be operative in juvenile hypertension are involving either volume control (by renal regulation of sodium-chloride and water balance) or vasoactive substances like the kallikrein-kinin, the renin-angiotensin and the prostaglandin system and other less well defined hormones. There is a close interrelationship of all these hormones with each other as well as a close linking of these vasoactive compounds to the renal regulation of sodium-chloride and water balance, thus interfering with a major environmental factor necessary for the development of essential hypertension. At present, data are insufficient to delineate a single hormone or a single hemodynamic abnormality as the only primary factor in juvenile hypertension. Further research into the pathomechanisms responsible for the elevation of blood pressure at its very beginning will improve our understanding of hypertension and possibly benefit its management by early intervention.

Child↗
PubMed1980

Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during a mackerel diet.

Eicosapentaenoic acid (C20:5 omega 3), which is present in high concentration in certain salt-water fish, may reduce the incidence of cardiovascular disease in Greenland Eskimos by reducing platelet aggregation and adhesion. Changes in platelet and plasma fatty acids, platelet aggregation, and thromboxane (TX) formation were studied in 7 healthy White men who had been on a mackerel diet for 1 week. Platelet aggregation had TX synthesis after low-dose collagen stimulation in platelet-rich plasma were reduced. This could be due to the marked change of the ratio of C20:5 to arachidonic acid (C20:4 omega 6) in platelet membranes. When the men were on the mackerel diet, their C20:5 level in platelet membranes and in plasma increased and that of C20:4 dropped. Both fatty acids were released during platelet aggregation. The reduction in the amount of C20:4 liberated and/or a diminished conversion of C20:4 to TXA2 by competitive inhibition of the platelet cyclo-oxygenase by the released C20:5 could be responsible for the decreased platelet aggregation.

Animals↗