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Biomedical subjects

H Engelberg

Publications and source records attributed to H Engelberg.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of UDP-glucuronosyltransferases in rat liver microsomes by natural mutagens and carcinogens.

Eight toxic compounds of natural origin present in the human diet or used as drugs were tested as inhibitors of UDP-glucuronosyltransferase (UGT) activity in rat liver microsomes with 1-naphthol (1-NA), phenolphthalein (PPh) and 4-nitrophenol (4-NP) as substrates. Strong inhibitory effects were observed with tannic acid (tannin) and the antifungal drug griseofulvin (GF): at a concentration of 1 mM, the two compounds completely suppressed the glucuronidation of 1-NA and PPh, respectively. A concentration of 0.1 mM still proved to be highly inhibitory, and even at a concentration as low as 50 microM, tannin produced nearly 50% inhibition of 1-NA conjugation. The UGT isoforms converting 4-NP were less sensitive to the tested compounds (with the exception of GF). Kinetic studies with tannin revealed an uncompetitive type of inhibition toward 1-NA, with an apparent Ki value of 20 microM. The inhibition by GF was non-competitive with respect to PPh and was of a mixed type toward UDP-glucuronic acid, with apparent Ki values of 40 microM and 30 microM, respectively. Tannin and GF did not act as substrates for rat microsomal UGT.

Animals↗
PubMed2001

Endogenous heparin activity deficiency: the 'missing link' in atherogenesis?

This paper reviews published studies since 1995 dealing with many atherogenic mechanisms where exogenous heparin was beneficial. In these areas endogenous heparin deficiency is likely to be harmful. Mechanisms included inflammatory factors, lower endogenous plasma heparin levels, lipoprotein lipase, chemokines, APOE e4, lipoprotein(a), among others. Demonstrated reduction of heparan sulfate proteoglycans (HSPG) and of endogenous plasma heparin was reviewed.

Animals↗
PubMed1999

Actions of heparin that may affect the malignant process.

BACKGROUND: Heparin has many actions that may affect the malignant process, especially metastasis. METHODS: The author conducted an extensive review of the available medical literature about heparin activity that may apply to important factors involved in the malignant process. RESULTS: Thrombin is generated by tumors, and the resultant fibrin formation impedes natural killer cell activity. Microthrombi arrest tumor cells in capillaries. Heparin prevents the formation of thrombin and neutralizes its activity. Angiogenesis has an important role in metastasis; heparin minimizes angiogenesis via the inhibition of vascular endothelial growth factor, tissue factor, and platelet activating factor. It decreases tumor cell adhesion to vascular endothelium as it inhibits selectin and chemokine actions, and it also decreases the replication and activity of some oncogenic viruses. Matrix metalloproteinases, serine proteases, and heparanases have an important role in metastasis. Heparin decreases their activation and limits their effects. It competitively inhibits tumor cell attachment to heparan sulfate proteoglycans. It blocks the oncogenic action of ornithine decarboxylase and enhances the antineoplastic effect of transforming growth factor-beta. Heparin inhibits activator protein-1, which is the nuclear target of many oncogenic signal transduction pathways, and it potently inhibits casein kinase II, which has carcinogenic activity. Platelet-derived growth factor, which has oncogenic effects, is also inhibited by heparin, as are reverse transcriptase, telomerase, and topoisomerase prooncogenic actions. CONCLUSIONS: These various heparin actions justify clinical investigation of its possible beneficial effect on malignant disease.

Anticoagulants↗
PubMed1997

Evidence that endogenous heparin activity deficiency may be an important factor in atherogenesis.

Known atherosclerotic risk factors account today for only 50% of atherogenesis. Evidence is presented that a deficiency of endogenous heparin may account for the other half. Sensitive techniques have shown that there are trace quantities of heparin in plasma of humans. An inverse relationship has been found between plasma heparin levels and triglyceride-bearing Sf 12-400 lipoprotein, and a lower plasma heparin level could be an important determinant of atherogenesis fostering lipid abnormalities. Endogenous heparin also protects endothelium from harmful mediators that can impair normal function. Since atherosclerosis is a chronic inflammatory disease process, with monocyte-mediated release of cytokines and activation of integrins and phospholipase A2-mediated generation of platelet activating factor, heparin inhibits many of these events. Endogenous heparin activity thus opposes the effects of inflammatory activators. Heparin is also kown to inhibit complement activation and to suppress endothelin release from endothelial cells. In addition, endogenous heparin may suppress smooth muscle cell proliferation and decrease microthrombi formation on injured endothelial sites. All of these data seem to suggest that a deficiency of endogenous heparin or heparin-like substances predipose to atherosclerosis. It is conceivable that a genetically determined endogenous heparin deficiency is involved in atherosclerosis.

Adult↗
PubMed1992

Low serum cholesterol and suicide.

Primary prevention trials which have shown that the lowering of serum cholesterol concentrations in middle-aged subjects by diet, drugs, or both leads to a decrease in coronary heart disease have also reported an increase in deaths due to suicide or violence. There has been no adequate explanation for this association. I have reviewed the relevant published work and describe a physiological mechanism that might account for this curious finding. One of the functions of serotonin in the central nervous system is the suppression of harmful behavioural impulses. When mouse brain synaptosomal membrane cholesterol is increased there is a pronounced increase in the number of serotonin receptors. Low membrane cholesterol decreases the number of serotonin receptors. Since membrane cholesterol exchanges freely with cholesterol in the surrounding medium, a lowered serum cholesterol concentration may contribute to a decrease in brain serotonin, with poorer suppression of aggressive behaviour.

Antisocial Personality Disorder↗
PubMed1991

Low-dose intermittent heparin therapy decreases plasma fibrinogen levels.

Elevated plasma fibrinogen levels, even in the "normal" range, have been shown to be an important predictor of myocardial infarcts and strokes. In the past 2 years 29 patients with coronary atherosclerotic disease were started on intermittent SC heparin therapy. The dose varied but in most instances was 10,000 units 3 times/week or 15,000 units twice a week (nonanticoagulant doses). Coagulable plasma fibrinogen decreased in 22 of the 29 patients, and the decrease was greater in those with initially higher levels. The decline usually was gradual and continuous. The results were statistically (paired t test) very highly significant (p = 0.0006).

Coronary Disease↗
PubMed1983

Serum lipemia: an overlooked cause of tissue hypoxia.

This article discusses an overlooked subject, namely that serum lipemia affects the transfer of oxygen from the blood to the tissues. It discusses several mechanisms whereby lipemia limits oxygen diffusion. Observations of improved tissue oxygenation in atherosclerotic patients coincident with the clearing of lipemia by heparin are described. Conversely, the adverse effects of increased lipemia after fat meals upon tissue oxygen are noted. The contribution of hypoxia of the arterial wall to atherogenesis is outlined, and its adverse effects in the ischemic heart are listed.

Angina Pectoris↗
PubMed1980

Heparin and atherosclerosis. A review of old and recent findings.

This article reviews the experimental and clinical evidence regarding heparin therapy in the prophylaxis of coronary heart disease. The actions of heparin take place at the vascular endothelium where injected heparin concentrates, and within the bloodstream. At the endothelium heparin acts to prevent endothelial injury, prevent thrombin generation, prevent platelet adhesion to endothelium, and to decrease uptake of serum lipoproteins. Within the bloodstream heparin increases lipoprotein lipase activity and reduces the concentration of atherogenic very low-density lipoproteins. The reduction in lipemia enhances oxygen transfer from blood to the tissues, and decreases thrombin or ADP-induced platelet aggregation. Heparin increases the concentration of high-density lipoproteins. It decreases hypercoagulability and inhibits overactivation of serum complement. Heparin reduced atherosclerosis in most studies in cholesterol-fed animals. In human subjects who had a myocardial infarct at least one year before the onset of treatment, long-term intermittent heparin therapy significantly decreased cardiovascular deaths as compared to control groups.

Animals↗