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Biomedical subjects

H P Wolff

Publications and source records attributed to H P Wolff.

At least 19 recordsLinked to original sources
PubMed1992

[Medical use of fetal cells and tissue: ethical aspects].

After considering the moral status of the living and of the dead human fetus, the article examines various ethical arguments connected with the use of fetal remains following elective abortion: financial or humanitarian incentives for the termination of pregnancy, conflicts of interest between mother and user, authority over fetal remains and modality of donation and utilization of the fetus. To prevent improper use of fetal remains it is recommended: to separate completely the decisions relating to abortion (first) and to the subsequent use of fetal tissues (second); to obtain explicit informed consent from the mother, making it impossible for her to direct any specific use of the fetal tissues; to base decisions on the method and timing of an abortion on the mother's health care needs alone; to exclude those involved in the process of abortion from any use of the fetus; to protect the anonymity of donor and recipient through an intermediary (tissue bank).

Abortion, Induced↗
PubMed1990

Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677).

A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the EC50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig much greater than mouse greater than rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate greater than pyruvate greater than alanine much greater than propionate greater than glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (EC50 = 0.85 mM) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.

Animals↗
PubMed1988

Irreversible inhibition of the TXA2/PGH2 receptor of human platelets by a photoaffinity ligand.

In order to tag the TXA2/PGH2 receptor of human platelets, we synthesized azido-BSP (= 4-[2-(4-azido-benzenesulfonylamino)-ethyl]phenoxyacetic acid), a photolabile derivative of the specific TXA2/PGH2 receptor antagonist sulotroban (= BM 13.177). If protected from UV light, azido-BSP competitively inhibited the shape change of human washed platelets stimulated by the TXA2 mimetic U 46619. Schild analysis revealed a pA2 = 6.7 (apparent KD = 0.2 mumol/l). Irreversible inhibition of the U 46619-induced platelet activation was achieved by irradiating for 5 min with UV light of 254 nm a platelet suspension containing azido-BSP. After subsequent washing, the platelets were stimulated with U 46619, ADP or PAF. Under these conditions azido-BSP inhibited the shape change, aggregation and [3H]serotonin release induced by U 46619 but not the shape change induced by ADP or PAF. The concentrations of azido-BSP which blocked the U 46619-induced [3H]serotonin release and the aggregation were 0.5 mumol/l and 1.0 mumol/l, respectively, whereas even 50.0 mumol/l of azido-BSP only partially inhibited the U 46619-stimulated shape change. Obviously, increasing numbers of thromboxane receptors have to be blocked in order to inhibit the [3H]serotonin release, the aggregation and the shape change. Even at an azido-BSP concentration equal to 250 times the apparent dissociation constant, enough receptor sites remained active to allow U 46619 to induce the shape change. In sulotroban was added prior to irradiation, the blocking effect of azido-BSP decreased with increasing concentrations of sulotroban. These results show that azido-BSP is a specific and high affinity ligand of the TXA2/PGH2 receptor and that it covalently links to the receptor under irradiation. Azido-BSP is a new tool to identify and characterize the TXA2/PGH2 receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1985

Synthesis and hypoglycemic activity of N-alkylated hydrazonopropionic acids.

A series of N-alkylated 2-hydrazonopropionic acids have been synthesized and evaluated for their hypoglycemic activity. Most of the compounds exhibit a remarkable blood glucose lowering activity in fasted guinea pigs. Some of the structural variables studied were the effects of branching, unsaturation, or substitution on the alkyl side chain and the effect of nuclear substitution on the aralkyl analogues. From these compounds, 2-[[(E)-2-methyl-3-phenyl-2-propenyl]hydrazono]propionic acid (BM 42.304; 42) was selected for further investigation.

Animals↗
PubMed1984

The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug.

BM 13.177 (4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid) is a representative of a new class of sulfonamidophenylcarboxylic acids which possess platelet-inhibitory and anti-thrombotic activity and inhibits the contraction of rabbit aorta stimulated by PG endoperoxides and TXA2. BM 13.177 5 mg/kg body weight p.o. protected rabbits from arachidonate-induced sudden death and greater than or equal to 10 mg/kg dose-dependently reduced the experimental thrombus formation induced in the rabbit aorta by perivascular administration of silver nitrate. In guinea-pigs, the collagen-induced bronchoconstriction was inhibited in a dose- and time-dependent fashion. The formation of TXA2 and the TXA2-induced platelet aggregation and smooth muscle contraction are probably crucial events in these experimental models. The protective effect of BM 13.177 may, therefore, be due to the TXA2-antagonizing effect of BM 13.177, which has been conclusively demonstrated in human platelets (PATSCHEKE and STEGMEIER, Thrombosis Res., 33, 277-288 (1984). The antagonism of TXA2 is supported by the observation that BM 13.177 also specifically inhibits the contraction of isolated arterial strips from rabbits which were stimulated with the thromboxane A2 mimetic U 46619. Schild-plot with a slope close to unity suggests a competitive type of antagonism. BM 13.177 exhibited neither anti-inflammatory nor ulcer-inducing activity of cyclooxygenase inhibitors. Furthermore it did not block the TXB2 formation in spontaneously clotting blood from rabbits and did not inhibit the release of prostacyclin-like activity from rabbit aortas. The lack of toxicological effects in long-term toxicity studies in rat and dog, together with the absence of objective and subjective side effects in the first human studies have encouraged us to initiate clinical trials in order to evaluate the therapeutic benefit of this new approach in humans.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1979

[Renal kallikrein-kinin system and control of blood pressure (author's transl)].

Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.

Angiotensin II↗
PubMed1979

Urinary kallikrein in normotensive subjects and in patients with essential hypertension.

1. Excretion of urinary kallikrein was normal in 13 out of 15 patients with uncomplicated essential hypertension. 2. Frusemide increased urinary kallikrein excretion in normotensive subjects and in patients with essential hypertension. The stimulating effect of frusemide on urinary kallikrein was significantly diminished in patients with essential hypertension. 3. No correlations of urinary kallikrein with sodium, potassium, and aldosterone excretion were found. 4. The results do not support the idea that urinary kallikrein plays a primary role in the pathogenesis of essential hypertension.

Adult↗
PubMed1978

Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension.

The relationship between sympathetic responsiveness and the blood pressure reduction induced by long-term beta-blockade was assessed in patients with essential hypertension. The increase in plasma noradrenaline concentration during physical exercise was used as an index of sympathetic responsiveness. The cardioselective beta-blocker, atenolol, was given to 16 patients with sustained benign essential hypertension for five weeks at a dose of 200 mg/day. Atenolol induced a marked decrease in blood pressure and pulse rate during recumbency, orthostasis and exercise concomitant with a marked increase in plasma noradrenaline concentration (p less than 0.0125) and a pronounced decrease in plasma renin concentration (p less than 0.01). The ratio of plasma noradrenaline during exercise to the base line concentration correlated significantly with the subsequent decrease in mean arterial blood pressure induced by beta-blockade (r = 0.840; p less than 0.001). A less significant correlation was observed between the plasma renin concentration and the subsequent decrease in mean arterial pressure (r = 0.542; p less than 0.05). The results obtained indicate that sympathetic responsiveness is an important determinant of blood pressure response to beta-blockade induced by atenolol.

Adrenergic beta-Antagonists↗
PubMed1978

Plasma noradrenaline and the pressor action of exogenous noradrenaline in normotensive subjects and patients with essential hypertension.

1. An inverse relationship was found between plasma noradrenaline and reactivity to exogenous noradrenaline in normotensive subjects. 2. The relationship between plasma noradrenaline and reactivity was distrubed in age-matched patients with essential hypertension. 3. A multiple-regression analysis showed a highly significant correlation between adrenergic activity and reactivity to noradrenaline and the mean arterial blood pressure level (r = 0.91). The results suggest that adrenergic activity and pressor response to noradrenaline combined are important determinants of arterial blood pressure. 4. An inverse relationship could also be demonstrated between plasma renin activity and reactivity to exogenous angiotensin II. No difference was observed between normotensive and hypertensive subjects.

Adult↗