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P Ney

Publications and source records attributed to P Ney.

35 records · Page 2Linked to original sources
PubMed1989

Endothelial protection by defibrotide--a new strategy for treatment of myocardial infarction?

Myocardial ischemia is associated with endothelial injury and an apparently insufficient generation of endothelium-derived vasodilating and platelet and white cell inhibitory mediators, such as prostacyclin (PGI2) and EDRF. This paper reviews some recent findings of our laboratory on cardioprotective effects of defibrotide, a PGI2 stimulating agent, in experimental myocardial ischemia and its possible sites of action in several in vitro assay systems. Defibrotide (32 mg/kg x h) reduced the infarct size by 50% in pigs, subjected to 1 h of coronary artery ligation followed by 3 h of reperfusion. This was associated with significant inhibition of neutrophil activation during the reperfusion period and a two-to threefold increase in cardiocoronary PGI2 generation. In vitro studies on PAF- and calcium ionophore-stimulated human granulocytes confirmed a dose-dependent (10-1000 micrograms/ml) antineutrophil effect of defibrotide (inhibition of lysosomal enzyme release) which was independent of the type of stimulus. Defibrotide (0.1 mg/ml) also inhibited superoxide anion generation from PAF stimulated neutrophils in Langendorff-perfused guinea pig hearts and was equipotent to a specific PAF antagonist (BN 52021). Defibrotide (0.1 mg/ml) did not stimulate PGI2 release from cultured porcine aortic endothelial cells but enhanced PGI2 release four- to fivefold above control if endothelial cells were coincubated with platelets. These data demonstrate a considerable cardioprotective potential of defibrotide which appears to involve endothelial protection from granulocyte-derived noxious compounds and a long-lasting stimulation of PGI2 production.

Animals↗
PubMed1988

The thromboxane receptor antagonist, daltroban, protects the myocardium from ischaemic injury resulting in suppression of leukocytosis.

The cardioprotective action of the new selective inhibitor of thromboxane receptors, daltroban (BM 13.505), was studied in cats subjected to 3 h of coronary artery ligation followed by 2 h of reperfusion. In comparison with vehicle (physiological saline)-treated cats, daltroban (20 mg/kg per h i.v.) reduced the ischaemia-induced rise in the ST segment and prevented the development of a Q-wave in the ECG during reperfusion. This was paralleled by a significantly improved preservation of creatine-phosphokinase activity in the ischaemic myocardium. Daltroban significantly attenuated platelet ATP secretion, the U-46.619-induced contraction of the cat thoracic aorta ex vivo and the myeloperoxidase-associated generation of reactive oxygen species ex vivo. These effects could be largely attributed to the inhibition of ischaemia-induced leukocytosis. It is concluded that daltroban protects the myocardium from ischaemic injury and that this effect involves prevention of ischaemia-induced leukocytosis.

Adenosine Triphosphate↗
PubMed1988

Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation.

This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.

Alprostadil↗
PubMed1988

Potent inhibition of leukotriene (LT) B4 release from human polymorphonuclear leukocytes (PMN) by the PGE1-analogue OP-1206.

The present study investigates the inhibitory action of the PGE1-analogue OP-1206 on stimulated LTB4 release from human PMN. In comparison with PGE2, PGE1 and iloprost, OP-1206 was equipotent to PGE2 and PGE1 as inhibitor of PAF (3 microM) and FMLP (10 microM) induced LTB4 release even in the presence of exogenous arachidonic acid (10 microM). Iloprost was ineffective in this assay at a concentration of 10 microM. The data together with earlier observations suggest that E-type prostaglandins are potent inhibitors of receptor-mediated PMN activation and that these compounds may be valuable for prevention of PMN-associated tissue damage.

Alprostadil↗
PubMed1988

Protection of the ischaemic myocardium from reperfusion injury by defibrotide and its possible mechanism of action.

The following study was designed to investigate the therapeutic value of defibrotide (32 mg/kg bolus + 32 mg/kg x h i.v.) in a cat model of acute myocardial ischaemia (MI) and reperfusion and to elucidate its possible mechanism(s) of action. Infusion of defibrotide (DEF), starting 30 min after the onset of ischaemia, had no effect on any of the hemodynamic parameters measured. In comparison with vehicle-treated animals, DEF largely attenuated the MI-associated ST-segment elevation and completely prevented the development of a pathological Pardee-Q-wave upon reperfusion. Furthermore, DEF largely antagonized the loss of creatine phosphokinase from the ischaemic reperfused myocardium. DEF significantly reduced the MI-induced thrombocytopenia and inhibited the collagen-induced platelet ATP-secretion ex vivo. Interestingly, DEF-treatment did not modify the MI-induced leucocytosis or the release of reactive oxygen radicals from activated neutrophils. These findings indicate that stimulation of endogenous prostacyclin formation by DEF reduces myocardial reperfusion injury independently of any direct effects of the compound on neutrophil activation.

Animals↗
PubMed1987

Biosynthesis of 1-alkenes in higher plants. A model study with the composite Carthamus tinctorius L.

Uneven numbered 1-alkenes, such as 1-pentadecene, 1-heptadecene, 1,8-heptadecadiene, 1,8,11-heptadecatriene and 1,8,11,14-heptadecatetraene are the predominant hydrocarbons in germinating safflower (Carthamus tinctorius L.). According to their chain length and positions of double bonds they are derived from palmitic, stearic, oleic, linoleic or linolenic acid, respectively. This has been proved by administration of synthetic alpha-, beta-, or gamma-deuterated 12-phenyldodecanoic acids to germinating safflower. Mass spectrometric analysis of the resulting deuterium-labelled 11-phenyl-1-undecenes shows that only a single hydrogen from C-3 and carbon dioxide from C-1 of the precursor fatty acid is lost during vinyl group formation. A strong isotope effect (kH/kD greater than or equal to 10) during the conversion of racemic 12-phenyl[3-2h]dodecanoic acid to 11-phenyl-1-[2-2H]undecene is consistent with an initial enzymatic attack on a non-activated hydrogen at C-3 accompanied by simultaneous fragmentation into the respective 1-alkene and carbon dioxide. Mechanisms, based on ionic or radical abstraction of a hydrogen from C-3 of the fatty acid, followed by decarboxylation are discussed. The results are applicable to the formation of various vinylic substituents in natural products such as porphyrins, acetylenic hydrocarbons, pheromones from marine brown algae and terpenoids.

Alkenes↗
PubMed1985

Homosexuality.

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Homosexuality↗
PubMed1985

Abortion.

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Abortion, Legal↗
PubMed1981

Thymic dysfunction in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is, in the great majority of cases, a neoplastic proliferation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigations reported herein, we further demonstrate the immune deficiency of CLL by measuring proliferation and immunoglobulin synthesis in response to mitogens. Stimulation of various cell fractions indicates that in certain cases there is deficient T-helper, while others T function appears intact. In 2 of 4 cases tested there was augmentation of ig synthesis when the CLL cells were cocultured with thymic epithelium. The implications of such in vitro modulation are discussed.

Aged↗
PubMed1979

Relationship between abortion and child abuse.

Although permissive abortion has been advocated on the grounds it will reduce the prevalence of child abuse and infanticide, there is no evidence to prove it has. There is a growing concern that it may have contributed to the problem. This article outlines eight possible methods whereby an increasing rate of abortion will lead to an increasing rate of abuse. There is evidence that an abortion results in depression which hinders mother-infant bonding in a subsequent pregnancy. An abortion of the first pregnancy may interrupt the developing bonding mechanism and interfere with the ability to bond to the next infant. If the hypothesis is correct, medicine by endorsing abortion on request may be jeopardizing the safety and care of a large number of children.

Abortion, Induced↗